Diagnosing, prognosing, and early detection of cancers by dna methylation profiling

ABSTRACT

A method of employing DNA methylation analysis for the diagnosis, prognosis, and prediction of cancer.

GRANT SUPPORT Flight Attendants Medical Research Institute (C.J.M & M.D.M), NIH (R01CA078609, R01CA100679, R01CA52689, P50CA097257), National Cancer Institute (R01CA126939, R01CA105274); National Institutes of Environmental Health Sciences (T32ES007155, P42ES05947); NIEHS/NCI (ES/CA06409); International Mesothelioma Program at Brigham and Women's Hospital (Research grant); Mesothelioma Applied Research Foundation (Research grant). R01 ES006717-09A2 (PI: JKW) R01CA126831-01A2 (PI: JKW). National Cancer Institute (R01 CA126939) and NIEHS (T32ES007155, P42ES05947). NIHCA89032 (JLW). The is government has certain rights in this invention.

FIELD OF THE INVENTION

A method of employing DNA methylation analysis for the diagnosis, prognosis, and early detection of cancer.

BACKGROUND OF THE INVENTION

Without being bound by any particular theory, a widely accepted tenet of cancer biology states that cancer is clonal, with tumors arising as the result of expansion of increasingly dysregulated cells. This insight led to the paradigm that selective expansion of cells with a growth advantage occurs in an ordered fashion, driven primarily by genetic changes [1]. This model has expanded to now include the thesis that cancers also evolve a “mutator phenotype” and become malignant as a result of somatic genetic events [2]. While this is believed that some cancers are induced by mutagens (e.g. tobacco smoke and ionizing radiation), these carcinogens as well as those that are not mutagenic (or are very poor mutagens) may be also be acting to induce epigenetic alterations. In fact, it is well recognized that carcinogens may induce dysregulation of the somatic epigenome, and thereby crucially contribute to cancer development. The term epigenetics refers to changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence. These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.

Significant epigenetic events, including DNA hypermethylation-induced gene silencing, are believed to be contributors to carcinogenesis. Methylation associated gene silencing occurs when certain cytosines in specific clustered regions primarily located in gene promoters are hypermethylated. These regulatory CpG islands often occur in tumor suppressor genes and are thought to remain largely unmethylated in noncancerous cells. Approximately half of all human genes contain CpG islands. Three loci are subject to this type of aberrant silencing [3]. Recent technologic advances allow for the simultaneous resolution of hundreds of specific, phenotypically defined cancer-related methylation events, providing a platform for the rapid epigenetic profiling of gene silencing in human tumors [4].

Malignant pleural mesothelioma is a rapidly fatal malignancy. It is associated with asbestos exposure in approximately 80% of patients [5]. In the United States, Great Britain, and Japan, over 5000 cases occur annually and median survival of patients with pleural mesothelioma is less than one year [6,7,8]. The economic burden of treating this disease and the litigation associated with asbestos exposure is estimated to exceed $265 billion over the next four decades in the United States [9]. Despite the decline in asbestos use among industrialized nations, the incidence of mesothelioma continues to rise, and it is not expected to peak until 2020, as disease latency can be as long as fifty years [10]. Importantly, asbestos is currently mined and exported throughout the world, with heavy use evident in developing nations such as China, India, and Central America [11]. Asbestos-containing products are still imported to the U.S., and many asbestos exposure hazards remain from earlier applications; one well publicized example being dust from the World Trade Center towers collapse in New York City [12]. A more complete understanding the molecular-genetic consequences of asbestos exposure and the mechanism of action of these mineral fibers in inducing mesothelioma is critically needed to develop more effective approaches for identifying and treating this devastating disease.

The causal link between asbestos and pleural mesothelioma has been widely accepted since 1960 [13], and the carcinogenic mechanisms of asbestos have been investigated in earnest since that time; establishing a view that asbestos fibers are not point mutagens, but rather both clastogenic and cytotoxic in vitro [14,15]. Additionally, methylation-induced tumor suppressor gene silencing has been observed in recent studies of mesothelioma [16,17,18,19,20] leading to the hypothesis that asbestos fibers contribute to epigenetic silencing of tumor suppressor genes in this disease. Consistent with this, Tsou et al. observed a significant association between self-reported asbestos exposure and methylation at the MT1A, and MT2A gene loci in mesotheliomas [18]. Using quantitative asbestos body counts as a measure of asbestos exposure burden has revealed an association between cell cycle control tumor suppressor gene methylation and increased asbestos burden in mesothelioma [20].

Research indicates that somatic mutations [21] and alterations in gene expression [22] are a feature of this disease. Interestingly, relatively few pathologically important mutations arise in this cancer, and there is no currently identified characteristic somatic genetic change attributed to the action of asbestos [21]. Further, although there is consensus that gene expression (at the mRNA level) is significantly altered in mesothelioma, there is no currently identified gene expression signature representative of the action of asbestos in this disease. There remains a debate about the clinical significance of mRNA expression profiling [23,24,25].

Shared signs and symptoms of these diseases include malignant pleural effusion, dsypnea, chest-pain, and fatigue [26,27]. An enhanced description of the character of the underlying somatic alterations, and thereby a proper diagnosis, is of paramount importance, especially considering the disparate prognoses and treatment regimens for lung adenocarcinoma and mesothelioma [28,29].

Several techniques have been used or proposed for differential diagnosis. Cytologic approaches to differential diagnosis have historically had a wide margin of variability in sensitivity depending on sample preparation methods and feature sets analyzed [30,31]. Currently, the most common method employs an immunohistochemical panel containing both epithelial and mesothelial markers [32]. Despite recent improvements in antibody panels for differential diagnosis, there is no consensus immunohistochemical panel or evidence-based guidelines for panel selection [32,33]. Another method, using mRNA expression gene ratios has reported differential diagnosis accuracy of 95% and 99% for mesothelioma and adenocarcinoma respectively [34]. The instability of mRNA, though, may make wide-scale implementation of this technology challenging, particularly outside of major academic surgical centers.

It is well recognized that promoter DNA hypermethylation is a mechanism of stable control of transcription, and an important contributor to carcinogenesis. When certain cytosines in specific clustered regions primarily located in gene promoters are hypermethylated, aberrant, stable gene silencing can occur. Regulatory CpG clusters are common, often occur in tumor suppressor genes, and are thought to remain largely unmethylated in noncancerous cells. In fact, about half of all human genes contain CpG islands and are potentially subject to aberrant methylation silencing [3,35]. Recently, the simultaneous resolution of hundreds of specific, phenotypically defined cancer-related is CpG methylation marks has become technologically feasible, allowing for rapid, high-throughput epigenetic profiling of human tissue CpG methylation [4]. In examining DNA methylation cellular DNA, any source of cells from the tissue of interest will suffice. Biopsied cells of suspect masses is an option. For pleural cancers pleural fluid is a likely source. It will be clear to those of skill in the art that in particular instances cell samples may be obtained from, without limitation, blood or blood fractions, cerebrospinal fluid, stool, saliva, bone marrow, urine, perspiration, amniotic fluid, lymph, and excised tissue.

SUMMARY OF THE INVENTION

The invention is an assay useful in the diagnosis, prognosis, and early detection of human cancers. Further, there is a use for this assay in predicting response to treatment for certain cancers. In conducting the assay of the invention, DNA methylation profiles are obtained from tumor DNA and from non-tumor DNA from patients and compared. The DNA methylation profiles obtained from tumor cells has been demonstrably distinct from DNA methylation profiles of non-tumor cells. Furthermore, differences between tumor types can be valuable for differential diagnosis, and differences within tumors of a given type can be informative of tumor etiology and or prognosis. Finally, early detection of cancers is possible.

The instant invention comprises a method for the diagnosis or prognosis of cancer in a subject comprising

(a) obtaining DNA methylation data from DNA of a subject's cells wherein said cells are suspected of being cancerous (Subject DNA methylation data);

(b) comparing said Subject DNA methylation data to a library of Tumor Control DNA methylation data and a library of Normal Control DNA methylation data (each representing same tissue of origin);

(c) fitting by mixture modeling P(Y,C) Subject DNA methylation data to said

Tumor and Normal Control DNA methylation data using recursively partitioned mixture modeling (RPMM) in conjunction with an empirical Bayes procedure generating a posterior probability distribution P(C|y*) of methylation class membership for Subject DNA y*,

Said Subject DNA methylation data's identity with Normal Control being indicated by posterior probability of membership P(C=k|y*) at least 90% in a class k comprised of at least 95% Normal Control samples [P(control|C=k)>95%];

(d) establishing a metric-based criterion for comparison by computing mean methylation average beta values μ_(j) at each CpG locus j from said Normal Control DNA methylation samples data y_(ij) and fitting the distribution of squared weighted Euclidean distances d_(i) ²=Σ{(y_(ij)−μ_(j))²/[μ_(j)(1−μ_(j))]} to a gamma distribution G, and where said Subject DNA methylation data's squared weighted Euclidean distance d*²=Σ{(y_(j)*−μ_(j))²/[μ_(j)(1−μ_(j))]} is less than the 95% quantile of G it is indicated with at least 95% certainty that the subject's sample is Normal and if the subject's squared weighted Euclidian distance d*² is greater than the 95% quantile of G it is indicated with at least 95% certainty that the subject's sample is a tumor.

In the practice of the instant method steps (c) and (d) above are non-limiting examples of methods for establishing metric-based criteria for data of this type. Empirical Bayes procedures and distance metrics based on distributions from libraries of Control DNA methylation data will yield the assignment of the identity of a subject's sample as cancerous or normal with at least about 70% accuracy, and particularly at least about 80% accuracy and more particularly at least about 90% accuracy.

The instant method is also applicable to prognosis. In cancer prognosis a subject's sample, if cancerous, is further studied by applying steps (c)/(d) above to the Tumor Control DNA methylation sample data only. The subjects' prognosis will be equivalent to the history of subjects from which Tumor Control DNA methylation data was derived having distribution of class membership greater than about 90%. Here, of course, it is understood that useful Tumor Control DNA methylation data for this aspect will include clinical follow-on histories of subjects diagnosed with cancer and particular to such cancers.

We note that mu is the mean of average betas across multiple samples at a given CpG. A metric-based criterion for comparison is made by computing the mean of average array methylation values (mean of average beta values at a CpG locus j to give μ_(j)) and a distribution of u for all CpG loci j equivalent to G.

The invention is exemplified and supported below for several different tumor types and an immunologic application including without limitation:

-   -   1. Diagnosis and prognosis of pleural mesothelioma.     -   2. Differential diagnosis of mesothelioma and lung         adenocarcinoma.     -   3. Diagnosis and prognosis of head and neck cancer.     -   4. Diagnosis and prognosis of bladder cancer.     -   5. Diagnosis and prognosis of lung cancer.     -   6. Differential diagnosis and early detection of childhood         leukemia.     -   7. Enumerating the numbers and ratios of immune cells within         peripheral blood and malignant and non-malignant tissues for         early detection and diagnosis.

In addition to these applications, other cancers may be diagnosed and/or prognosed using the assay of the invention. Such cancers include malignant and benign tumors of the connective tissue, the endothelium, the mesothelium, blood, lymph cells, muscle, epithelial tissue, neural tissue, APUD (amine precursor uptake and decarboxylation) system and neural crest derived cell (pigment producing cells in the skin and eyes, Schwann cell, merkel cells) tumors. More specifically, such tumor related cancers include fibrosarcoma, myxoma, lipoma, chondroma, osteoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, chordoma, fibrous and malignant fibrous histiocytoma, hemangiosarcoma, angiosarcoma, lymphangioma, lymphangiosarcoma, myeloproliferative disorders, leukemias, plasmacytosis, plasmacytoma, multiple myeloma, Hodgkin and Non-hodgkin lymphoma, leiomyoma, leiomyosarcoma, rhabdomyoma, rhabdomyosarcoma, papilloma, seborrheic keratosis, squamous cell carcinoma, epidermoid carcinoma, benign and malignant skin adnexal tumors, adenomas and adenocarcinomas of the liver, kidney, or bile duct, choriocarcinoma, seminoma, embryonal cell carcinoma, anaplastic and multiforme gliomas, neuroblastoma, medulloblastoma, ganglioneuroma, benign and malignant meningioma, benign and malignant tumors of the nerve sheath, basophilic, eosinophilic, chromophobe and parathyroid adenomas and carcinomas, C cell hyperplasia, medullary carcinoma of the thyroid, benign and malignant tumors of the pancreas, stomach, intestines, carotid body and chemo-receptor system, Sertoli-Leydig cell tumors, germ cell tumors, cystosarcoma phylloides, Wilms tumor and fibroadenoma.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Unsupervised clustering of average beta values in tumor and non-tumor pleura.

Using the R software package normal tissue sample average beta values were subjected to unsupervised hierarchical clustering based on Manhattan distance and average linkage. Each column represents a sample and each row represents a CpG locus (750 most variable autosomal loci). Above the heatmap black indicates a tumor sample, and white indicates a non-tumor pleural sample. In the heat map white=average beta of zero, or unmethylated, and black=average beta of one, or methylated.

FIG. 2. Beta mixture model of methylation profiles in mesothelioma and non-tumor pleura.

Methylation average β is white for unmethylated and black for methylated. Methylation profile classes are stacked in rows separated by horizontal lines, and class height corresponds to the number of samples in each class. Class methylation at each locus is a mean of methylation for all samples within a class. Bar charts display the proportion of tumors and non-tumor pleura samples in each class. Methylation profile classes differentiate tumor from non-tumor pleura (P<0.0001).

FIG. 3. Beta mixture model of methylation profiles in pleural mesothelioma. Methylation average β is white for unmethylated and black for methylated. Methylation profile classes are stacked in rows separated by horizontal lines, and class height corresponds to the number of samples in each class. Class methylation at each locus is a mean of methylation for all samples within a class. On the left, bar charts show proportions for gender and tumor histology among samples within each class. On the right, box plots of log asbestos body counts for each class. Controlling for gender, methylation class membership predicts asbestos burden (P<0.03).

FIG. 4. Unsupervised clustering heatmap of CpG loci in all samples and tumors only.

Unsupervised hierarchical clustering heat map based on Manhattan distance and average linkage of the 500 autosomal CpG loci with the highest variance. Columns are samples, rows are CpG loci. Black indicates methylated and white indicates unmethylated A) All samples, color coded bars indicate sample type B) Tumor samples only.

FIG. 5. Recursively partitioned mixture model of CpG methylation for lung adenocarcinomas, mesotheliomas, and non-malignant pulmonary tissues.

The figure depicts the results of RPMM. Columns represent CpG sites and rows represent methylation classes. The height of each row is proportional to the number of observations residing in the class, and the color of the columns within the row represents the average methylation of the CpG for that class. Black indicates methylated and white indicates unmethylated. Pie charts represent the composition of the group of classes indicated with respect to tissue type. Methylation profile classes differentiate sample types (permutation test P<0.0001).

FIG. 6. Recursively partitioned mixture model of CpG methylation for lung adenocarcinomas and mesotheliomas.

The figure depicts the results of RPMM. Columns represent CpG sites and rows represent methylation classes. The height of each row is proportional to the number of observations residing in the class, and the color of the columns within the row represents the average methylation of the CpG for that class. Black indicates methylated and white indicates unmethylated. Pie charts represent the composition of the group of classes indicated with respect to tissue type. Methylation profile classes significantly differentiate tumor types (permutation test P<0.0001).

FIG. 7. (A) Unsupervised hierarchical clustering and heatmap of methylation beta values for 1250 most variable loci across all samples. (B) Recursive partitioning mixture model classification of normal and tumor head and neck tissues using all methylation beta values resulting in 8 classes whose average methylation beta values are represented in the heat map. Distribution of normal and tumor samples within each class is depicted in pie charts on the right.

FIG. 8. Recursive partitioning mixture model classification of head and neck squamous cell carcinomas (A) resulting in 6 classes with average methylation beta values across loci depicted in the heatmap. (B) Average age of (C) lifetime average packs of cigarettes smoked per day by, (D) distribution of tumor location of, and (E) lifetime average alcoholic drinks per week consumed by patients whose samples are members of the distinct methylation classes depicted in (A).

FIG. 9. A) Recursively partitioned mixture model of normal bladder and bladder tumor tissues. Methylation class three is comprised exclusively of normal bladder tissues and bladder tumor samples are distributed among remaining classes. B) Venn diagram identifying 65 CpG loci in common across three separate approaches to analyzing the methylation profiles between bladder tumors and normal bladder tissues.

FIG. 10. A) Scatter plot indicating the propensity for increased methylation among invasive bladder tumors relative to non-invasive tumors in two separate case series studies of disease. B) Recursively partitioned mixture model of each series of bladder tumor samples. C) Genes and CpG loci identified which overlap between two separate approaches to ascertaining the most critical loci with differential methylation between invasive and non-invasive bladder cancer.

FIG. 11. Unsupervised hierarchical clustering of DNA methylation data from 1400 autosomal CpG loci in lung tumor and non-tumor lung tissues. On the heatmap, white corresponds to an average beta of zero (unmethylated), and black corresponds to an average beta of one (methylated). Above the heatmap black bars indicate tumor samples and white bars indicate non-tumor lung samples.

FIG. 12. Recursively partitioned mixture model of DNA methylation data from lung tumor and non-tumor lung tissue samples. Black indicates methylated and white indicates unmethylated. Methylation class height corresponds to the number of samples in a class and the mean of average beta values within each class are displayed in columns.

FIG. 13. Recursively partitioned mixture model of methylation data from autosomal CpG loci in squamous cell carcinomas of the lung.

FIG. 14. Clustering heatmap using linear models were fitted for each CpG site on the leukemia subtype to derive differences between all pairs of subtypes. Patient samples clustered vertically, and gene CpGs horizontally (gene names along the right hand site). Black are unmethylated, white, methylated, grey intermediate. Moderated t-statistics & the associated p-values were calculated, as well as B-statistics, the log posterior odds ratio that a gene is differentially methylated (DM) versus not DM. The 40 CpGs with FDR<0.05 were used for clustering analysis. Leukemia subtypes in grayscale above the clustering heatmap: note that TEL-AML1 (30% black) completely clusters independently, as do hyperdiploid, and hyperdiploid RAS+, separately (50%, 60% black respectively). E2A-PBX1 (black) is distinct from the others.

FIG. 15. A) Plot of locus-by-locus analysis of CpG methylation in infant bloods from controls compared to infant bloods from individuals who went on to develop leukemia; P-values versus linear regression coefficients where negative coefficients correspond to reduced methylation in cases relative to controls. B) The distributions of the sum of the top 19 most differentially methylated CpG loci between cases and controls, indicating significantly higher methylation in controls relative to cases (P=5.0×10⁻¹³).

DETAILED DESCRIPTION OF THE INVENTION Example 1

The invention is useful for diagnosis and prognosis of malignant pleural mesothelioma. The present invention characterizes phenotypically significant alterations in the epigenome of mesothelioma. Enumerated is the epigenetic status of over 800 genes believed to be cancer-related, and wherein such genes are believed to stably control mRNA expression. The invention entails comparing normal pleura with mesothelioma pleural tissue. Data suggest that a large number of loci are epigenetically altered in mesothelioma, that asbestos exposure is associated with the degree of epigenetic alteration, and that profiles of gene silencing are associated with clinical outcome. This work demonstrates that the epigenome is a primary point of pathogenic effect of asbestos exposure in the genesis of mesothelioma.

To comprehensively investigate tumor-specific, phenotypically relevant methylation events in pleural mesothelioma, 158 tumors were profiled. Also 18 non-tumorigenic parietal pleura samples were profiled. Profiling was for methylation at 1505 CpG dinucleotides associated with 803 cancer-related genes. Profiling was done by methylation bead array (Illumina, Inc., GoldenGate Genotyping Assay®, San Diego Calif.). Data delineate the relationship between a comprehensive, phenotypically important CpG methylation profile and disease status. It also provides tumor methylation profiles which permit an association with patient clinical course and carcinogen (e.g., asbestos) exposure.

Choice of Study Population

In one example of tumor study population tumor material was obtained following surgical resection at Brigham and Women's Hospital through the support of the International Mesothelioma Program. Similarly, grossly non-tumorigenic parietal pleura samples were taken as residual tissue during extrapleural pneumonectomy from uninvolved anatomic sites. Patients were drawn in near equivalent numbers from a pilot study conducted in 2002 (n=70), and an incident case series beginning in 2005 (n=88). Among identified cases the participation rate was 85%. All patients underwent surgical resection prior to other treatments. Clinical information, including histologic diagnosis, was obtained from pathology reports. Each patient was assessed for history of exposure to asbestos as well as additional demographic and environmental data by obtaining their medical and occupational history with an in-person questionnaire or interview. Additionally, the study quantified asbestos bodies in samples of lung tissue from multiple sites in the resected lung [36] [37]. Each tumor was pathologically examined and the amount of tumor in every sample estimated by direct microscopic evaluation and recorded as the percent tumor for that specimen. Patients were followed for survival using the National death index and last known clinic visit.

Methylation Analysis (Applies to all Examples)

Tumor and non-tumor pleural DNA was extracted from frozen tissue using the QIAamp DNA mini kit according to the manufacturer's protocol (Qiagen, Valencia, Calif.). DNA was modified by sodium bisulfite to convert unmethylated cytosines to uracil using the EZ DNA Methylation Kit (Zymo Research, Orange, Calif.) according to the manufacturer's protocol. To characterize the epigenetic profile of mesothelioma and non-tumorigenic parietal pleura we used the Illumina GoldenGate® bead array that simultaneously interrogates 1505 CpG sites associated with 803 cancer-related genes to generate a methylation value based upon ˜30 replicate measurements for each locus in each sample. The Illumina array interrogates approximately two CpGs per gene and although sequencing methods would provide additional details, CpGs were cultivated from reports which have demonstrated the methylation-expression relationship in large is part through sequencing experiments. Bead arrays have a similar sensitivity as quantitative methylation-specific PCR and were run at the UCSF Institute for Human Genetics, Genomics Core Facility according to the manufacturer's protocol and as described by Bibikova et al [4].

Analysis of Tissue Sample Methylation

Exposure, demographic and tumor characteristic data for mesothelioma and non-tumor pleura are presented in Table 1 below.

TABLE 1 Subject gender, age, histology and exposure for mesothelioma patients and non-tumor pleural samples. Mesothelioma Pleura patients donors Gender, n (%) Female  38 (24)  4 (22) Male 120 (76) 14 (78) Age Range  30-80 38-77 Mean (sd)  62 (9.8) 58 (11.3) Histology, n (%) Epithelioid 116 (73) — Mixed  37 (23) — Sarcomatoid  5 (3) — Asbestos exposure, n (%) Yes 112 (74) 13 (72) No  39 (26)  5 (28) Log Asbestos Body Available n (%) 108 (68) — Range  0-5.5 — Mean (sd)  2.16 (1.18) —

Array methylation data were first examined with unsupervised hierarchical clustering using Manhattan distance and average linkage for the 750 most variable autosomal CpG loci (FIG. 1). Striking differences between the epigenetic profiles of mesothelioma and non-tumor pleura are observed, with almost perfect clustering of epigenetic profiles based on disease status. Next, in a univariate approach, we tested all CpG loci individually for an association between methylation and disease status, and 969 CpG loci had methylation levels that differed (Q<0.05) comparing tumor and non-tumor pleura following FDR correction. Of these, 727 loci associated with 493 genes had enhanced methylation in non-tumor pleura, and 242 loci associated with 153 genes had more methylation in the tumors (Supplemental Table 1).

Since so many loci were differentially methylated between tumor and non-tumor pleura, we next applied a modified model-based form of unsupervised clustering known as mixture modeling. This approach built classes of samples based on profiles of methylation with data from all autosomal loci using a mixture of beta distributions to recursively split the tumors into parsimoniously differentiated classes [38,39,40]. All posterior class membership probabilities were numerically indistinct from 0 or 1. Applying a beta mixture model to methylation data from all autosomal loci in tumors and non-tumor pleura returned eleven methylation classes, their average methylation profiles, and their sample type distributions (FIG. 2). Methylation class membership was a highly significant predictor of diseased versus non-diseased tissue (permutation P<0.0001). Among the 11 classes in the model, 9 classes perfectly captured only tumor or only normal, and there were 2 methylation classes containing both tumor and normal samples. To follow up, a supervised random forest classification of non-tumor and tumor samples was performed. Only 1 tumor (<1%) was misclassified as a non-tumor sample, and 5 non-tumor samples (28%) were misclassified as tumors. The overall misclassification error rate was 3.4%, significantly lower than the expected error rate under the null hypothesis (P<0.0001).

We next restricted our analyses to tumors, (n=158) first applying our beta mixture model approach. Seven methylation classes resulted. See FIG. 3. This figure also displays the distributions of gender, histology, and asbestos body counts by methylation class. Methylation class membership was not a significant predictor of patient gender or tumor histology (data not shown). Again, methylation profile class membership was not associated with the amount of tumor in the sample. However, methylation class membership significantly predicted lung asbestos body count (permutation P<0.04). Since men with pleural mesothelioma have higher asbestos body counts compared to women (P<0.0001) [41] we controlled for gender, and methylation class membership remained a significant predictor of asbestos burden tested for associations between methylation and asbestos body counts; consistent with our prior data,[20] tumor methylation average β values at CDKN2A (P<0.02), CDKN2B (P<0.02), and RASSF1 (P<0.03) were significantly and positively associated with asbestos body counts. In addition, methylation of MT1A (previously reported as asbestos exposure-associated by Tsou et al. [18]) was significantly positively associated with asbestos burden; promoter associated CpG49 (P<0.04), and exonic CpG13 (P<0.02). When testing all autosomal loci for an association between methylation and asbestos burden using the MTA1 promoter CpG 49 Q-value (Q=0.32) as a cutoff, there were 110 loci with an association between methylation status and asbestos burden (Supplemental Table 2). The vast majority of these 110 loci (94%) had a positive correlation between CpG methylation and asbestos body counts, indicating gene silencing was the dominant phenotype associated with asbestos associated epigenetic change.

Lastly, we examined the relationships between methylation profiles and patient outcome using Cox proportional hazards models of survival controlling for age, gender, and tumor histology. Median survival time of this population was 12.5 months with 67 months of follow-up time. In a proportional hazards model including all cases (n=158), women had half the risk of death of men (HR=0.5, 95% CI, 0.3-0.96), and patients with mixed histology tumors were at greater risk of death compared to those with epithelial tumors (HR=2.7, 95% CI, 1.7-4.4). Importantly, methylation class membership was also a significant predictor of patient outcome (P<0.01). In particular, membership in methylation classes four and seven were both independently associated with a significant 3-fold increased risk of death compared to the class with the lowest median asbestos count (95% CIs, class four: 1.4-7.0, class seven: 1.3-7.4) (Table 2). Where data were available (n=108), and after adjustment for methylation class membership, asbestos burden was associated with a significant 1.4-fold increased risk of death (95% CI, 1.1-1.8) (See Table 2 below). In this model, membership in methylation class four remained associated with a significant, nearly 3-fold increased risk of death (HR=2.8, 95% CI, 1.1-7.1). Again, in this model including asbestos exposure, likelihood ratio tests indicate that methylation classes were significant predictors of patient outcome (P<0.005).

TABLE 2 Gender, tumor histology, methylation profile class membership, and asbestos burden are predictors of pleural mesothelioma patient survival. All Cases Cases with asbestos burden data n (%) n (%) Co-Variate Total n = 158 HR 95% CI P-value Total n = 108 HR 95% CI P-value Age, mean (sd)  62 (9.8) 1.02  1.0-1.05 0.09  61 (9.5) 1.03 1.0-1.1 0.18 Gender Male 120 (76)  1.0 (reference) — 84 (78) 1.0 (reference) — Female 38 (24) 0.5  0.3-0.96 <0.04 24 (22) 1.5 0.6-3.5 0.38 Histology Epithelial 109 (69)  1.0 (reference) — 74 (68) 1.0 (reference) — Mixed 44 (28) 2.7 1.7-4.4 <0.0001 31 (29) 2.1 1.2-3.8 <0.02 Sarcomatoid 5 (3) 2.8 0.95-8.2  0.06 3 (3) 1.2 0.3-5.2 0.83 Asbestos burden, mean (sd) — — — — 2.2 (1.2) 1.4 1.1-1.8 <0.04 Methylation Class 2 24 (15) 1.0 (reference) — 17 (16) 1.0 (reference) — 1 22 (14) 1.4 0.6-3.4 0.47 10 (9)  0.5 0.1-2.2 0.37 3 28 (18) 0.9 0.4-2.0 0.75 19 (18) 0.4 0.1-1.2 0.11 4 24 (15) 3.1 1.4-7.0 <0.01 24 (22) 2.8 1.1-7.1 <0.03 5 24 (15) 1.4 0.6-3.5 0.44 17 (16) 0.9 0.3-2.8 0.89 6 17 (11) 2.0 0.8-5.4 0.16 11 (10) 1.2 0.3-4.8 0.79 7 19 (12) 3.1 1.3-7.4 <0.01 10 (9)  1.7 0.6-5.0 0.36 Controlled for all variables in table. model log liklihood P < 0.01 Controlled for all variables in table. Classes 1 to 7 corresppond top to bottom from FIG. 3 model log liklihood P < 0.005

Statistical Analysis (Applies to all Examples)

BeadStudio Methylation software from the array manufacturer Illumina (SanDiego, Calif.) was used for dataset assembly. All array data points are represented by fluorescent signals from both M (methylated) and U (unmethylated) alleles, and methylation level is given by β=(max(M, 0))/(|U|+|M|+100), the average methylation (β) value is derived from the ˜30 replicate methylation measurements and a Cy3/Cy5 methylated/unmethylated ratio. At each locus for each sample the detection P-value was used to determine sample performance, three samples (2%) with >25% of loci having a detection P-value>1e−5 were dropped from analysis. Similarly, CpG loci with a median detection P-value>0.05 (n=8, 0.5%), were eliminated from analysis.

Subsequent analyses were carried out using the R software [42]. For exploratory and visualization purposes, hierarchical clustering was performed using R function hclust with Manhattan metric and average linkage. Associations between sample type, or covariates such as age or gender and methylation at individual CpG loci were tested with a generalized linear model (GLM). The beta-distribution of average beta values was accounted for with a quasi-binomial logit link with an estimated scale parameter constraining the mean between 0 and 1, in a manner similar to that described by Hsuing et al. [43]. CpG loci where an a priori hypothesis existed were tested independently. In contrast, array-wide scanning for CpG loci associations with sample type or covariate used false discovery rate correction and Q-values computed by the qvalue package in R [44].

For inference, data were clustered using a mixture model with a mixture of beta distributions, and the number of classes was determined by recursively splitting the data via 2-class models, with Bayesian information criterion (BIC) used at each potential split to decide whether the split was to be maintained or abandoned as described in [45]. Permutation tests (running 10,000 permutations) were used to test for association with methylation class by generating a distribution of the test statistic for the null distribution for comparison to the observed distribution. For continuous variables, the permutation test was run with the Kruskal-Wallis test statistic. For categorical variables we used a Chi Square test statistic. Significant associations from permutation tests were controlled for potential confounders where appropriate using logistic regression with methylation classes and potential confounders and a likelihood ratio test of the model with and without methylation classes. For survival analyses, Cox proportional hazards models were utilized, and likelihood ratio tests were used to examine the significance of inclusion of the methylation classes in the models.

The R Package was also used to build classifiers with the Random Forest (RF) approach. RF is a tree-based classification algorithm similar to Classification and Regression Tree (CART) [46] and was performed on CpG average beta values using RandomForest R package version 4.5-18 by Liaw and Wiener. RF builds each individual tree by taking a bootstrap sample (sampling with replacement) of the original data and on average about ⅓ of the original data are not sampled (out of bag or OOB). Those sampled are used as the training set to grow the trees, and the OOB data are used as the test set. At each node of the tree, a random sample of m out of the total M variables is chosen and the best split is found among the m variables. The default value for m in the Random Forest R package is √M. In this analysis we will test a range of m from half of √M to two times the √M and will use the m that gives the lowest prediction error. The OOB error rate is the percentage of time the RF prediction is incorrect.

Example 2

Differential diagnosis of lung adenocarcinoma and pleural mesothelioma was performed using DNA methylation profiles in the context of non-malignant pulmonary tissues.

Our previous work has demonstrated hundreds of differentially methylated CpG loci in pleural mesothelioma compared to non-diseased pleura [47]. Other reports, using a small number of candidate loci, have demonstrated significant differences in gene-promoter methylation prevalences between lung adenocarcinoma and mesothelioma [19,48].

In this study we exploited the stability of the aberrant cytosine methylation mark and new array-based technology for high throughput measurement of DNA CpG methylation to investigate the methylation status of 1413 autosomal CpG loci associated with 773 cancer-related genes on Illumina's GoldenGate methylation bead-array platform as described above.

Choice of Study Population

Using one of the largest case series studies of these diseases and focusing on epigenetic alteration, we demonstrate that methylation profiling can differentiate lung adenocarcinoma, mesothelioma, and non-malignant tissues. Lung adenocarcinomas (n=57) and non-malignant pulmonary tissues (n=48) (and a subset of non-tumor tissues (n=22 (39%)) were from the adenocarcinoma patients) were from patients treated for NSCLC at the Massachusetts General Hospital from 1992-1996 [49]. Additional normal lung tissues were obtained from the National Disease Research Interchange from donors free of lung malignancy (n=4). Mesotheliomas (n=158) and grossly non-tumorigenic parietal pleura (n=18) were obtained following surgical resection at Brigham and Women's Hospital through the International Mesothelioma Program. Patients were drawn in near equivalent numbers from a pilot study conducted in 2002 (n=70), and an incident case series beginning in 2005 (n=88); among identified cases the participation rate was 85%. All patients provided informed consent under the approval of the appropriate Institutional Review Boards. Clinical information, including histologic diagnosis was obtained from pathology reports.

Analysis of Tissue Sample Methylation

Demographic and tumor characteristic data for these samples are presented in Table 3.

TABLE 3 Patient demographics, exposures, and tissue characteristics Lung Pleura Co-variate Non-tumor (n = 52)^(a) Adenocarcinoma (n = 57)^(b) Non-tumor (n = 18)^(c) Mesothelioma (n = 158)^(d) Age Range 47-89 35-89 38-77  30-84 Mean (SD) 68.8 (9.2) 68.2 (11.4) 58.3 (11.3)   61.7 (9.8) Gender (n) % Male 26 (55.4) 23 (40.4)  14 (77.8) 120 (75.9) Female 21 (44.6) 34 (59.6)  4 (22.2)  38 (24.1) Histology (n) % Adenocarcinoma — 57 (100) — — Epithelioid — — — 109 (69.0) Biphasic — — —  44 (27.8) Sarcomatoid — — —  5 (3.2)^(e) Smoking status Current 15 (28.8) 18 (31.6) —  34 (27.2) Former 27 (51.9) 27 (47.3) —  43 (34.4) Never  5 (9.6) 12 (21.1) —  48 (38.4) Asbestos^(f) No 41 (89.1) 55 (98.2)  5 (27.8)  39 (25.9) Yes  5 (10.9)  1 (1.8) 13 (72.2) 112 (74.1) ^(a)Five samples missing age and gender data, 6 samples missing exposure data. ^(b)One sample missing asbestos exposure data ^(c)No smoking data available. ^(d)33 missing smoking data, 7 missing asbestos exposure data. ^(e)Excluded from tumor only analysis ^(f)Occupational exposure (lung), known exposure (pleura)

Mean age and gender distributions were similar between tumor and their non-tumor samples of origin. Lung adenocarcinomas and non-tumor lung samples had similar exposures to smoking, and did not have significantly different asbestos exposure history. Mesotheliomas had similar exposure to asbestos as non-tumor pleural samples.

Unsupervised hierarchical clustering of the 500 most methylation-variable autosomal CpG loci revealed readily apparent differences in the epigenetic profiles among lung adenocarcinoma, mesothelioma and non-malignant tissues (FIG. 4A). However, non-malignant pleural and pulmonary tissues do not appear to segregate well from each other. An unsupervised hierarchical clustering of tumors only is shown in FIG. 4B. We next applied a modified model-based form of unsupervised clustering known as recursively partitioned mixture modeling (RPMM) [45]. The RPMM returned 17 methylation classes whose average methylation profiles are shown in FIG. 5; 11 of these classes (68%) perfectly captured a single sample type, and methylation profiles were a significant predictor of tissue sample type (P<0.0001). The 50 CpG loci whose methylation status most effectively discriminates among these 17 methylation classes are listed in Supplemental Table 3.

A supervised random forests (RF) classification of methylation data in all samples was used to follow up on results from the RPMM. RF classification was used because it allows for growing classification trees with a training set drawn from the whole dataset, leaving about one-third of samples out to serve as the test set for generating an unbiased estimate of classification error [50]. RF classification returned a confusion matrix showing which samples are correctly classified, those that are misclassified, and the misclassification error rate for each sample type (Table 4).

TABLE 4 Random forests analysis confusion matrices Lung Pleura Non-tumor Adenocarcinoma Non-tumor Mesothelioma Classification error Lung Non-tumor 47  4 1 — 9.6% Adenocarcinoma 1 56  — — 1.8% Pleura Non-tumor 7 — 5 6 66.7% Mesothelioma — 2 — 156 1.3% Overall error estimate = 7.0% P < 0.0001 Adenocarcinoma Mesothelioma Classification error Adenocarcinoma 56 1 1.75% Mesothelioma 1 152 0.65% Overall error estimate = 0.95% P < 0.0001

Overall, 20 samples were misclassified based on CpG methylation data, an overall misclassification error rate of 7.0%, significantly lower than the expected error rate under the null hypothesis (P<0.0001). Consistent with the observed patterns from unsupervised clustering, non-malignant tissues were more often misclassified (non-tumor misclassification error=24.3%), than tumors (misclassification error=1.4%). Of 52 non-malignant pulmonary tissues, 4 were confused as lung adenocarcinoma, and 1 as a mesothelioma (misclassification error=9.6%). Among 18 non-malignant pleural tissues, 7 were confused as non-tumor lung, and 5 as mesothelioma (misclassification error=66.6%). On the other hand, only one lung adenocarcinoma was misclassified, as a non-tumor lung (misclassification error=1.8%); and only 2 mesotheliomas were misclassified, both as lung adenocarcinoma (misclassification error=1.3%). The 50 most discriminatory CpG loci from this RF analysis are given in Supplemental Table 4.

We next restricted our analysis to lung adenocarcinoma and non-sarcomatoid mesotheliomas (n=210) and applied the RPMM approach (FIG. 6). In this model 14 methylation classes result, 12 of which (86%) perfectly capture one tumor type. Methylation classes are significant predictors of tumor type (P<0.0001). The 50 most critical loci for differentiating the methylation classes in this model are listed in Supplemental Table 5. Results were again followed up with random forests classification resulting in a confusion matrix with an overall misclassification error of <1%, (P<0.0001) (Table 4). Only one of each tumor type was misclassified as the other, and the 50 most discriminatory CpG loci for RF classification are given in Supplemental Table 6.

In a univariate approach, we tested all CpG loci individually for an association between methylation and tumor type with generalized linear models, followed by correction for multiple comparisons. In this manner, 1266 CpG loci had methylation levels that differed between lung adenocarcinoma and mesothelioma (Q<0.05, Supplemental Table 7). Among these 1266 CpG loci, 61% exhibited increased methylation in lung adenocarcinoma compared to mesothelioma, and 39% had higher methylation in mesothelioma.

Example 3

Diagnosis and prognosis of head and neck squamous cell carcinoma was investigated. Head and neck squamous cell carcinoma (HNSCC) is a physically, etiologically, and molecularly heterogeneous disease, with an annual incidence in the United States of over 40,000 cases. The majority of head and neck cancers are associated with tobacco and alcohol use, acting both independently and synergistically [51,52]. However, Human Papilloma Virus (HPV), particularly the high risk type 16, is associated with 20-25% of HNSCC, and individuals with HPV-positive disease compared to HPV-negative have better overall survival [53,54]. Given the established association of etiologic factors with clinical outcome, identifying the molecular character of tumors arising from varying exposures will aid in understanding the mechanisms influencing prognosis and provide novel targets for diagnosis and therapy of HNSCC.

Study of the contribution of epigenetic alterations to tumor biology is now a vast field, and it is widely accepted that epigenetic alterations in target tissues are part of the causal path to the development of malignancy[55,56]. DNA methylation-associated epigenetic silencing of tumor suppressor genes is an aberrant mark of cancer with considerable specificity. DNA hypermethylation in HNSCCs targets genes in pathways such as DNA repair, cell cycle control, apoptosis, angiogenesis, cell-cell interaction, and metastasis [57]. Associations among HPV16, smoking, betel nut use and methylation of specific genes have been identified [58,59,60]. These findings, though, have focused on single gene methylation alterations and their associations to exposures, but have not examined how exposures might be influencing the overall processes leading to epigenetic alteration. We have previously demonstrated that exposures and age, in bladder cancer, lead to an increased propensity for gene promoter hypermethylation in a panel of 16 tumor suppressor genes[61]. Using now available high-throughput technologies, we are better equipped to understand the process by which carcinogenic exposures act to alter the DNA methylation status of a developing tumor.

We aim to more completely understand the etiology of epigenetic alterations by examining the relationships between these alterations and carcinogen exposures. In this manner, we hope to define novel pathways through which HNSCC can arise, and aid in the development of diagnostic screening tools and targeted therapies. We characterized DNA methylation profiles of primary human HNSCC tumors by examining DNA methylation status of approximately 1400 CpG sites in about 800 cancer-related genes in a population-based case series of incident, primary HNSCC and non-diseased head and neck epithelium. Both the diagnostic and prognostic utility of these markers were defined; and uniquely, we also revealed how etiologic factors responsible for head and neck carcinogenesis are associated with the molecular character of these tumors.

Choice of Study Population

The study population has been previously described [58,62]. Briefly, incident cases of histologically confirmed HNSCC were identified from nine medical facilities in the Boston, Mass. metropolitan area. Diagnoses were confirmed by an independent study pathologist. All cases enrolled in the study provided written, informed consent as approved by the IRBs of the participating institutions. Archived pathology specimens were used for analysis of promoter hype rmethylation, and a total of 42 formalin-fixed paraffin embedded (FFPE) and 26 fresh frozen tumor samples were selected for analysis. Data on HPV16 tumor DNA status and serology from the parent case-control study [53] has been previously reported. Demographic and exposure information was collected through self-administered questionnaires, and clinical information through medical chart reviews.

Analysis of Tissue Sample Methylation

Table 5 shows the demographic characteristics of the final population studied. In addition to the case tumor tissues, non-malignant head and neck tissues from individuals without head and neck cancer were obtained from the National Disease Research Interchange (NDRI). Clinicopathologic information is limited by this is anonymous tissue bank, but all samples were obtained from patients who were not previously diagnosed with any cancer, and thus whose cause of death was not cancer related.

TABLE 5 Characteristics of the subjects with tissue involved in methylation analysis Non-diseased HNSCC Cases head and neck Characteristic (n = 68) tissues (n = 11) Age, mean (±SD) 57.6 (11.4) 66.2 (7.9) Gender, n (%) Female 14 (21%)  3 (27%) Males 54 (79%)  8 (73%) Sample Location, n (%) Oral 35 (52%)  3 (28%) Pharyngeal 26 (38%)  4 (36%) Laryngeal  7 (10%)  4 (36%) Cigarette Smoking¹, n (%) Never 16 (24%) — Former 38 (56%) — Current 13 (20%) — Lifetime Average Packs per  1.3 (0.5) — Day, mean (±SD)¹ Number of Years Smoking, 32.2 (14.5) — mean (±SD)¹ Lifetime Pack-years Smoked¹ 41.1 (26.1) — Lifetime Average Alcoholic 28.3 (35.5) — Drinks per Week Tumor HPV16 DNA Status² Negative 56 (85%) — Positive 10 (15%) — ¹Smoking data not available on 1 case and metrics of smoking (Average Packs Per Day, Years Smoked, and Pack-years smoked based only on

Characterization of the profile of DNA methylation alterations in non-malignant head and neck epithelial tissues compared to HNSCC tumor samples was completed using the IIlumina Goldengate Methylation BeadArray. Unsupervised hierarchical clustering of the DNA methylation data with Manhattan distance and average linkage as the metric across the 1250 most variable autosomal loci (FIG. 7 A) depicts relatively tight clustering of the non-malignant tissues compared to the tumors, as well as the extent of variability in the methylation β value across the loci. In a locus by locus analysis applying an FDR cut-off Q value of 0.05, we identified 261 loci with significantly differential methylation between tumors and normal (Supplemental Table 8). Of those, 125 loci showed greater methylation in tumors compared to normal, while 136 loci exhibited lower methylation levels in tumors compared to normal tissues. The confusion matrix (Table 6) resulting from random forest analysis shows which samples are correctly classified, those that are misclassified, and the misclassification error rate for each sample type.

TABLE 6 Random Forest Classification of Head and Neck Squamous Cell Carcinoma Tumor Status Using DNA Methylation Tumor Sample Non-disease Sample Error Rate Tumor Sample 66 2 2.90% Non-diseased Sample 5 6   45% Overall Out of the Box (OOB) Estimate of Error Rate = 8.86%, (Permutation test for association: P < 0.0001)

While 5 normal tissues (45%) were confused as tumors, only 2 tumors were misclassified as normal (3.0%), giving an overall error rate of (8.86%), a significant improvement in sample classification compared to the expected under the null hypothesis (P<0.0001). These results, consistent with our previous work, suggest that use of overall patterns of methylation alterations may have more utility in capturing the tumorigenic process than do individual alterations.

A recursive partitioning mixture model, applied to methylation data from all autosomal loci in tumors and non-tumor head and neck epithelial tissues delineated eleven distinct methylation classes (FIG. 7B). This model demonstrates that methylation class membership was a highly significant predictor of tumor status (permutation P<0.0001).

To examine how known risk factors for HNSCC are associated with these profiles, we utilized a case series approach, and re-constructed the recursive partitioning mixture models using only the tumor data (FIG. 8A), resulting in the delineation of six tumor specific classes. A permutation test with tumor stage, dichotomized as high (Stage III or IV) vs. low (Stage I or II) revealed a significant association between methylation Class membership and stage (P<0.01). A logistic regression model of stage (Supplemental Table 9) suggested that inclusion of methylation class is significant in predicting stage (likelihood ratio P<0.01), and that membership in Class 6 was associated with a significantly reduced risk of high stage disease (OR 0.1, 95% CI 0.01, 1.0). Membership in Class 2 showed a similar protective effect, while membership in Class 5 was associated with an increased risk of high stage disease, although the small numbers of tumors in these classes made these estimates unstable.

In order to identify if exposures leading to this disease are associated with these methylation classes, we examined the associations between individual risk factors for HNSCC and these classes. Methylation class was significantly associated with patient age as a continuous variable (Permutation Test P<0.01, FIG. 8B); methylation class 2 members had lower patient age, and class 4 higher age compared to other classes. Smoking intensity (packs per day) also significantly differed across methylation classes (P<0.04, FIG. 8C); Class 1 demonstrated lower smoking intensity, and 3 relatively high intensity. However, we did not observe a significant association of methylation class with smoking duration (years smoked) or pack-years smoked. A borderline significant association was observed with tumor site by methylation class (oral, pharyngeal, and laryngeal, P<0.1) (FIG. 8D). Tumor HPV16 DNA status also demonstrated an association with methylation class which approached statistical significance (P<0.1, FIG. 8E), patients in Class 4 had a greater prevalence of HPV positive tumors. Finally, lifetime average drinks per week also showed a strong differential trend by methylation class (P<0.1).

Multinomial logistic regression results are shown in Table 7, with the classes numbered as they were in FIG. 2A and with Class 5 serving as the referent class as this class had the largest membership. The overall Wald P-value indicates whether the covariate significantly differentiates class membership overall. Individual confidence intervals for each covariate within a class identify the magnitude of any association and significance of the association of a covariate on membership in that class compared to the referent class (Class 5), conditional on membership in either class.

TABLE 7 Multinomial Logistic Regression of Methylation Class Membership by Etiologic Factors Class 1 OR Class 2 OR Class 3 OR Class 4 OR Class 6 OR (95% CI) (95% CI) (95% CI) (95% CI) (95% CI) Covariate n = 17 n = 3 n = 4 n = 4 n = 17 Overall Wald P Age, per year

 

  Tumor Site

Oral Referent Referent Referent Referent Referent Pharyngeal 1.07 (0.93, 1.22)

0.98 (0.90, 1.06) 0.94 (0.88, 1.01) 0.90 (0.79, 1.01) Laryngeal

1.06 (0.95, 1.19) 0.98 (0.96, 1.01) 1.01 (0.92, 1.12) Tumor HPV16 DNA Status 0.32 Negative Referent Referent Referent Referent Referent Positive 1.00 (0.90, 1.11) 1.01 (0.95, 1.07) 0.98 (0.94, 1.01) 1.09 (0.98, 1.20)

Lifetime Avg. Packs of Cigarettes

  0.93 (0.85, 1.01) 1.07 (0.94, 1.22) 0.95 (0.85, 1.06) 0.92 (0.81, 1.04) 0.07 Per Day Smoked Lifetime Avg. Alcoholic Drinks Per

1.00 (0.99, 1.01) 1.01 (0.99, 1.02) 1.01 (0.99, 1.02)

Week Note: The Odds Ratio for each covariate in each class is conditional on membership in the given class compared to Class 5, the referent class (n = 23). The model is The model is controlled for all covariates listed in the table. Results in bold italics are considered statistically significant (P < 0.05).

Patient age, and average alcohol drinks per week each significantly differentiated membership across classes (Wald P<0.0001). Laryngeal tumors were less likely to be members of Class 1, and the odds of membership in Class 1 were significantly reduced with each year of age. In addition, the odds of membership in Class 1 compared to Class 5 were significantly decreased by almost 20% for each additional pack of cigarettes smoked per day on lifetime average. Each year of age reduced the odds of membership in Class 2 compared to Class 5 by greater than 10%, and tumors in this class were mostly likely to be oral tumors compared to pharyngeal or laryngeal. Only age demonstrated a significant effect on membership in Class 3 and Class 4, leading to a reduced odds of membership in Class 3 compared to Class 5, but an increased odds of membership in Class 4 compared to Class 5. Class 6 tumors were significantly less likely to be HPV positive tumors, but more likely to be from patients with greater lifetime alcohol exposures. These results overall suggest that differing etiologies of this disease influence the pattern of epigenetic alteration observed in the resulting tumors.

We examined if the DNA methylation profiles or methylation at specific loci were associated with patient survival. Amongst the 68 samples examined for methylation using the array, there were 22 deaths and a mean of 2.75 years of follow-up amongst surviving patients (range 0.75-5 years). We found no significant association between methylation classes derived from the RPMM procedure amongst tumors and overall patient survival, controlling for tumor stage and patient age.

Finally, we tested the hypothesis that biologic pathways, rather than overall profiles of methylation, are important in determining survival. To examine this hypothesis, we utilized Ingenuity Pathway Analysis to examine which specific pathways were over-represented amongst the top 500 loci having both positive and negative correlation with survival as determined by loci-specific Cox proportional hazards analysis [63]. The pathways identified to be significantly over-represented are listed in Table 8, as well as correlation between the increase in methylation beta value of the genes represented by that pathways and patient survival, such that those with a positive correlation would represent loci whose increasing methylation level is associated with improved patient survival (i.e. Hazard Ratio<1) while those with a negative correlation are loci where increasing methylation is associated with poorer survival or a risk hazard ratio (>1).

TABLE 8 Pathways significantly over-represented in analysis of loci-specific associations with patient survival Direction of Correlation with Pathway Survival P-value Genes on Array in Pathway Ephrin Receptor Signaling + 0.009 SRC, EGF, CRK, EPHA2, GNG7, PDGFB, FGF1 SAPK/JNK Signaling + 0.012 LCK, GADD45A, CRK, GNG7 PDGF Signaling + 0.02 SRC, PDGFRA, CRK, JAK3, PDGFB Cell Cycle: G2/M DNA Damage + 0.03 CDKN2A, GADD45A, CDKN1A, SFN Checkpoint Regulation NF-_(K)B Signaling + 0.039 LCK, BMP4, IL1RN, LTA, ZAP70, PDGFRA, EGF, IRAK3 p53 Signaling + 0.04 CDKN2A, GADD45A, CDKN1A, SERPINB5, BAX, SFN Acute Phase Response Signaling + 0.043 IL1RN, IL6, RBP1 Hepatic Fibrosis/Hepatic Stellate Cell + 0.045 IFNG, IFNGR2, EGF, MYH11, MMP2, BAX, IL6, Activation PDGFB, FGF1, COL1A1, CYP2E1, PDGFRA, TGFB3 Synaptic Long Term Depression − 0.045 IGF1, GUCY2D, PLA2G2A, NOS2A, NOS3, NPR2 Purine Metabolism − 0.049 TJP2, GUCY2D, PDE1B, NPR2

We also identified 18 loci with a false discovery rate less than 20% in their association with overall patient survival in models stratified by tumor stage and controlled for patient age, and those loci are shown in Supplemental Table 10. Of note, only 2 of these 18 loci (ZAP70 and GP1BB) are associated with a hazard ratio>1, while 16 demonstrate a protective HR<1. Such a negative association with risk could indicate, in fact, that loss of methylation at these loci may be associated with increased risk, as one might expect from oncogene activation.

Example 4

DNA methylation profiles were used to identify genes associated with invasive bladder cancer. In the United States in 2009, an estimated 71,000 cancers of the urinary bladder will be diagnosed and will result in greater than 14,000 deaths[64]. The vast majority of this mortality is attributed to high stage, invasive tumors that infiltrate the muscular layers of the bladder[65]. Lower stage, non-invasive disease, on the other hand, can be successfully treated, though this success comes at great economic burden to the healthcare system. Approximately 500,000 patients require monitoring in the U.S. leading to estimated diagnosis to death per patient costs ranging from $96,000 to $187,000, thereby resulting in $2.2 billion in annual expenditures, making bladder cancer the most expensive of all cancers[66,67]. Thus, cost-effective and prognostic strategies for disease detection and determination of recurrence or progression would be of significant clinical utility.

There is potential for the use of epigenetic alterations and particularly DNA CpG methylation as diagnostic markers for a variety of human cancers, including bladder cancers[68,69]. Hypermethylation of specific genes or families of genes including LAMA3 and the SFRP genes have been associated with invasive disease [70,71,72,73]. Additionally, using a panel of 16 genes, a propensity for hypermethylation in bladder cancers was associated with poorer patient survival[61]. Microarray-based approaches also have attempted to identify novel genes associated with invasive disease but with limited sample sizes due to the array strategy employed[74]. Array technologies which can examine specific CpG site methylation using sodium bisulfite modification strategies, considered the gold-standard of DNA methylation detection, allow for the rapid, cost-effective, and high-throughput determination of methylation status at greater than 1500 CpG sites across greater than 800 genes. Thereby, array approaches can be applied to population-based epidemiologic studies of utilizing large numbers of samples. This approach has established the DNA methylation status in diseases such as head and neck squamous cell carcinoma, malignant pleural mesothelioma, and lymphoma[47,75,76]. We have utilized this array-based approach to identify clinically and biologically informative patterns and novel targets of DNA CpG methylation in a population-based series of bladder transitional cell carcinoma.

Choice of Study Population

We utilized two, independent, non-consecutive population-based series of bladder cancer cases. The first, consisting of tumors from 73 individuals involved in a case-control study of incident bladder cancer in New Hampshire, enrolled between July 1994 and June 1998, has been previously described [77]. The second, consisting of tumors from 264 individuals enrolled between 2000 and 2004 in the New Hampshire portion of the New England Bladder Cancer Study, a population-based case-control study of incident bladder cancer in Maine, Connecticut, and New Hampshire, aimed at identifying the risk factors associated with an increased mortality from bladder cancer in New England. In both studies, all study participants provided written informed consent under the approval of the appropriate institutional review boards. Although separate in time and scope, these two studies utilized identical recruitment procedures, as well as identical protocols for the ascertainment of pathology materials for molecular examinations. Pathology reports and paraffin-embedded tumor specimens were requested from the treating physician/pathology laboratories. Bladder tumors were reviewed by the study pathology (A.R.S.) and classified according to the 1973 and 2004 World Health Organization guidelines for bladder tumors. The study pathologist identified the appropriate block from which the tumor samples used in these analyses were obtained, and the proportion of malignant cells in each sample was recorded. In addition, 5 samples of fresh-frozen, normal bladder epithelium from non-diseased individuals were obtained from the National Disease Research Interchange.

Analysis of Tissue Sample Methylation RPMM resulted in the clustering of these samples into 8 distinct classes (FIG. 9A) with a single class, class 3, containing all non-malignant bladder samples, and thus a significant difference in class membership by sample type (P<0.00001). We next determined the CpG loci which best differentiate methylation class 3 (containing the normal bladder tissues) from the other classes with AUG analysis (Supplemental Table 11). The confusion matrix resulting from the RF analysis (Table 9) demonstrates perfect classification of bladder tumor from non-malignant bladder epithelium (OOB error 0%).

TABLE 9 Confusion Matrix Resulting From Random Forest Classification of Bladder Tumor and Non-malignant Bladder Epithelium by DNA Methylation Profile Non-Malignant Bladder Tissue Tumor Classification Error Non-Malignant 5 0 0 Bladder Tumor 0 73 0 Note: Overall Out of the Box Error = 0%

Prominent loci for differentiating normal and tumorigenic bladder tissues in RF analysis (greatest percent change to the MSE;>5%) are listed in Supplemental Table 12. A locus by locus analysis of bladder tumor CpG methylation versus normal demonstrated that the average β values of 563 loci were significantly associated with tissue type at an FDR of <0.05 (listed in Supplemental Table 13). Of those 141 demonstrated higher average β values in tumors compared to non-malignant tissue, and 422 lower average β values in tumors. Loci with a q-value<1×10⁻⁶ (n=107), an AUC of ≧0.98, and a percent change to the RF MSE≧5% were compared and 65 loci were identified to overlap between these 3 approaches (FIG. 9B and Supplemental Table 14). Bisulfite pyrosequencing confirmed the methylation status of 3 of these loci in a subset of bladder tumors and all normal bladder epithelium samples (data not shown).

The status of DNA methylation average beta was compared between non-invasive and invasive bladder tumors in each of the 2 series of bladder cases independently and the average methylation beta values in each of these series comparing non-invasive to invasive tumors is depicted in FIG. 10A. These plots show highly similar patterns in both series, and both demonstrate general increased in methylation at numerous loci in invasive compared to non-invasive tumors. These results are confirmed in generalized linear models of examining the association of methylation beta with invasive tumor status in a locus by locus fashion, which demonstrated that 445 loci had significantly increased (FDR q<0.05) methylation and only 68 significantly decreased methylation in invasive compared to non-invasive tumors in series 1 and that 606 loci had significantly increased methylation and 41 significantly decreased methylation in invasive compared to non-invasive tumors in series 2. A list of these loci is provided as Supplemental Table 15.

RPMM revealed for each series, four classes (FIG. 10B) and the prevalence of invasive tumors in these classes was significantly different in each of the series (P<0.00001, permutation chi-square), with large proportions of invasive tumors in the class labeled 4 in each of the series. Using the AUC approach as before, we identified those loci, in each of the series that are most informative at distinguishing class 4 from the other 3 classes, and provide a table of those loci as Supplemental Table 16. A random forest approach at classification of invasive tumors, utilizing series 1 as a training set of methylation data and series 2 as an independent test set demonstrated an out of the bag error rate of 18% based on the training set. Using the classifiers developed from the training set on the test set resulted in overall error rate of 21% (Table 10).

TABLE 10 Confusion Matrices Resulting From Random Forest Classification of Invasive Bladder Tumors by DNA Methylation Profile with Series 1 as a Training Set and Series 2 as a Test Set Invasive Bladder Classification Non-Invasive Bladder Tumor Tumor Error Series 1-Training Set Non-Invasive Bladder 37  5 0.12 Tumor Invasive Bladder Tumor  8 23 0.26 Series 2-Test Set Non-Invasive Bladder 172  17 0.09 Tumor Invasive Bladder Tumor 38 37 0.51 Note: Overall Out of the Box Error on Training Set = 17.8% Test Set Overall Error Rate = 20.1%

Loci contributing a more significant percent change to the MSE (>5%) are listed in Supplemental Table 17. In series 1 and series 2, of loci with a locus by locus analysis q-value<0.001 (n=93 and 327, respectively), an RPMM AUG of >75% (n=103 and 122, respectively), and a percent change to the RF MSE≧6% (n=97 and 189, respectively), 5 loci were identified as overlapping across the 3 approaches and in both series of tumors (FIG. 10C; FRZB_E186_R, HOXB2_P99_F, KRT13_P676_F, RIPK1_P868_F, STAT5A_P704_JR).

Pyrosequencing assays for FRZB, STAT5A, KRT13, and HOXB2 were designed to examine the CpG examined on the array as well as 6 additional neighboring CpG sites for FRZB or 1 additional neighboring CpG sites for STAT5A and KRT13. There is were no neighboring CpG sites within the sequencing range of a pyrosequencing reaction for HOXB2. A subset of non-invasive (n=12) and invasive (n=11) bladder tumors examined on the array were sequenced for each of these loci. For all CpG sites examined, as well as the mean across sites for FRZB, KRT13, and HOXB2 we observed significantly greater methylation extent in invasive compared to non-invasive tumors, consistent with the array results. For STAT5A, we could confirm the significantly greater extent of methylation at the CpG site measured by the array in invasive compared to non-invasive tumors, but did not observe this association in the neighboring CpG sites.

In order to validate these results, we performed pyrosequencing for FRZB, KRT13, and HOXB2 in an independent series of bladder tumors (n=263) which were not examined in the array analysis and further evaluate patient survival as data for >10 years of follow-up was available in this series. Pyrosequencing results were successfully obtained for 248 samples at FRZB, 242 samples at HOXB2, and for 244 samples at KRT13. There was significant correlation between methylation extent at each of the individual loci examined in FRZB (P<0.0001, R²>0.8 for each CpG site compared to the other 6) and KRT13 (P<0.0001, R²=0.85) and thus we used the mean of the methylation across the sites for the subsequent analyses. The mean extent of methylation across all sites ranged from 0.98 to 97.8 (median 24.0) at FRZB, 14.5 to 92.0 (median 59.8) at KRT13, and for the single position examined at HOXB2 ranged from 0.0 to 91.5 (median 32.8).

Logistic regression models were used to examine the association between methylation extent at each of the loci, dichotomized at the median and invasive bladder cancer, controlled for patient age, gender, and TP53 immunohistochemical staining intensity, which has been previously associated with invasive disease[78,79]. Greater methylation extent of HOXB2 was strongly associated with invasive bladder cancer, independent of TP53 staining intensity (OR 7.7, 95% CI 3.3, 18.2), while greater methylation extent of neither KRT13 nor FRZB demonstrated a significant association. Further, in a logistic regression model including the methylation extent of all three of these loci and controlled for patient age, gender, and TP53 immunohistochemical staining intensity, HOXB2 was a significant risk factor for invasive disease (OR 8.6 95% CI 3.4, 21.7) adjusted for FRZB and KRT13 methylation and TP53 IHC staining intensity (Table 11).

TABLE 11 Associations Between Methylation of HOXB2, KRT13 and FRZB and Invasive Bladder Cancer Invasive Disease OR Noninvasive, n (%) Invasive, n (%) (95% CI) Total N 162 57 HOXB2 Methylation Negative (≦ median) 104 (93.7)  7 (6.3) 1.0 (referent) Positive (> median)  58 (53.7) 50 (46.3) 8.6 (3.4, 21.7) KRT13 Methylation Negative (≦ median)  86 (81.9) 19 (18.1) 1.0 (referent) Positive (> median)  76 (66.7) 38 (33.3) 1.0 (0.4, 2.3) FRZB Methylation Negative (≦ median)  84 (78.5) 23 (21.5) 1.0 (referent) Positive (> median)  78 (69.6) 34 (30.4) 0.9 (0.4, 2.0) TP53 IHC Staining Intensity Low (<3) 146 (84.9) 26 (15.1) 1.0 (referent) High (3+)  16 (34.0) 31 (66.0) 6.1 (2.7, 13.8) Note: Model is controlled for all variables in table as well as patient age and gender and includes all subjects with data on all 3 genes and TP53 IHC. We also examined combinations of methylation extent of these genes and found that having greater than the median methylation extent of both HOXB2 and KRT13 was associated with a statistically significant 8.5 fold (95% CI 2.6, 27.8) increased risk of invasive bladder cancer, compared to having neither methylation, and that methylation of either gene imparted an intermediate risk of invasive disease of 5.4 fold (95% CI 1.6, 17.8; P for trend<0.0003, Table 12).

TABLE 12 Methylation of Both KRT13 and HOXB2 is Independently Associated with Invasive Bladder Cancer Noninvasive, n (%) Invasive, n (%) Invasive Disease OR (95% CI) Total N 164 60 HOXB2 & KRT13 Methylation Neither Methylated  67 (94.4)  4 (5.6) 1.0 (referent) One Methylated  59 (74.7) 20 (25.3) 5.4 (1.6, 17.8) Both Methylated  38 (51.4) 36 (48.6) 8.5 (2.6, 27.8) TP53 IHC Staining Intensity Low (<3) 148 (85.1) 26 (14.9) 1.0 (referent) High (3+)  16 (32.0) 31 (68.0) 8.1 (3.7, 18.0) Note: Model is controlled for all variables in table as well as patient age and gender and includes all subjects with data on HOXB2 and KRT13 methylation and TP53 IHC. Trend test P < 0.0003.

There appeared to be dose-dependently poorer survival in those with either HOXB2 or KRT13 methylation extent>median and those individuals having both HOXB2 and KRT13 methylation extent>median, compared to those with both methylation extents≦median; Cox proportional hazards model (P for trend<0.03), with a 2.2 fold increased risk of death (95% CI 1.1, 4.6) among those having >median methylation extent at both of these loci, adjusted for patient age, gender, and TP53 IHC staining intensity (Table 13).

TABLE 13 Proportional Hazards Model of Survival in Bladder Cancer by Both HOXB2 and KRT13 Methylation n (%) HR (95% CI) HOXB2 & KRT13 Methylation Neither Methylated  73 (31.3) 1.0 (referent) One Methylated  85 (36.5) 1.5 (0.8, 3.1) Both Methylated  75 (32.3) 2.2 (1.1, 4.6) TP53 IHC Staining Intensity Low (<3) 177 (76.0) 1.0 (referent) High (3+)  56 (24.0) 1.0 (0.5, 1.9) Note: Model is controlled for all variables in table as well as patient age, gender, and tumor stage and includes all subjects with data on HOXB2 and KRT13 methylation and TP53 IHC. Trend test P < 0.03.

Example 5

DNA methylation profiles were used for differentiate lung tumors from normal lung tissue and predicting patient survival.

Choice of Study Population

Non-small cell lung tumors (n=114) and non-malignant lung tissues (n=48, matched to tumors) were from patients treated for NSCLC at the Massachusetts General Hospital from 1992-1996 [49]. Additional normal lung tissues were obtained from the National Disease Research Interchange from donors free of lung malignancy (n=4). All patients provided informed consent under the approval of the appropriate Institutional Review Boards. Clinical information, including histologic diagnosis was obtained from pathology reports.

Analysis of Tissue Sample Methylation

Unsupervised hierarchical clustering of all lung tumor and non-tumor lung tissues is presented in FIG. 11. The DNA methylation data at autosomal CpG loci for lung tumors (n=114) and non-tumor lungs (n=52) were modeled with a recursively partitioned mixture model (RPMM) and the resulting methylation profiles are displayed in FIG. 12. Lung tumors are distributed among 12 main classes, and non-tumor lung samples are distributed among three main classes. Only one lung tumor was present in one of the three main non-tumor lung methylation classes; and only one non-tumor lung sample was present in one of the lung tumor methylation classes. The DNA methylation profiles from RPMM significantly predict disease (P<0.0001). In a locus by locus comparison of CpG methylation in lung tumors versus non-tumor lung tissues (with patient-matched tumor/normal pairs removed) 1047 CpG loci were differentially methylated (Q<0.05; Supplemental Table 18). Among these 1047 CpG loci, 540 CpGs had increased methylation in tumors relative to normal lung samples and 507 CpG loci had increased methylation in normal lung tissue samples.

Next, squamous cell lung cancers were independently modeled with RPMM and nine methylation classes resulted (FIG. 13). Using a cox proportional hazards model of survival and controlling for patient age, gender and smoking status patients in methylation class 1 had significantly increased risk of death relative to patients in all other methylation classes (Table 14).

TABLE 14 Cox proportional hazards model of survival for squamous cell carcinoma of the lung RPMM methylation class membership (controlled for age, gender, stage, and smoking status). Methylation class Hazard Ratio P-value 1 1.0 referent 2 0.19 0.04 3 0.20 0.03 4 0.09 0.0002 5 0.19 0.02 6 0.10 0.01 7 0.09 0.04 8 0.03 0.002 9 0.10 0.01

Example 6

DNA methylation profiles were used in newborn infants to predict risk of developing leukemia and predicting both disease subtype and prognosis among cases.

The most common subtypes of childhood leukemia include proB-cell, cALL, and preB-cell. The most common molecular abnormality among pre-B cell leukemia is the t(1;19) E2A-PBX1 translocation which comprises about 25% of the subtype and about 5% of all pediatric ALL. The extent and timing of epigenetic alterations which contribute to the development of childhood leukemia are unknown. However, with readily available tumor cells from circulating blood, and the fact that these cancers develop early in life presents a unique opportunity for examining the potential of DNA methylation profiling in diagnosis, prognosis, risk assessment, and monitoring for disease.

We aimed to explore the potential for DNA methylation profiles to differentially diagnose specific leukemia subtypes, discover DNA methylation profiles which complement t(1;19) and other non-epigenetic molecular abnormalities with prognostic indications. Furthermore, in an examination of DNA methylation profiles from infant blood samples from individuals who went on to develop leukemia (n=30) and individuals who did not develop disease (n=20) we aimed to determine the ability of DNA methylation profiling in infants to inform risk of developing leukemia.

Choice of Study Population

Patients and Guthrie card infant blood samples were derived from the Northern California Childhood Cancer Study, an epidemiology study, and from the Children's Oncology DNA bank. Conventional karyotyping identified patients as t(1;19), and molecular cloning of the translocation provided confirmation [80]. All patient's parents provided informed consent, and the research was reviewed by the Institutional Review Board at UCSF.

Analysis of Sample Methylation/Analysis of Leukemias

Leukemia samples (n=53) were subjected to methylation analysis as described above in Example 1. Using recursively partitioned mixture modeling of DNA methylation data resulted in seven distinct methylation classes and leukemia subtype (cAAL/preB-cell) was significantly associated with methylation profile class membership (P<0.0001; Table 15).

TABLE 15 RPMM methylation classes in leukemia samples by disease type demonstrates a significant association between methylation profile and leukemia subtype (P < 0.0001). Methylation class cALL preB 1 0 10 2 1 2 3 0 4 4 6 18 5 3 1 6 4 0 7 4 0

Next, the association between specific molecular abnormalities and methylation profiles in these cases were explored by generating a clustering heatmap using linear models were fitted for each CpG site on the leukemia subtype to derive differences between all pairs of subtypes (FIG. 14). Moderated t-statistics & the associated p-values were calculated, as well as B-statistics, the log posterior odds ratio that a gene is differentially methylated (DM) versus not DM across distinct molecular abnormalities. The 40 CpGs with FDR<0.05 were used for clustering analysis. Leukemia subtypes in grayscale above the clustering heatmap: note that TEL-AML1 (30% black) completely clusters independently, as do hyperdiploid, and hyperdiploid RAS+, separately (50%, 60% black respectively). E2A-PBX1 (black) is distinct from the others.

Analysis of Infant Blood Samples

Next, infant blood samples from 30 patients who went on to develop leukemia and 20 infant blood samples from healthy individuals were subjected to methylation analysis as described above in example 1. In a locus-by-locus analysis of CpG methylation comparing infant bloods from cases to controls we found significantly reduced methylation in cases relative to controls (Supplemental Table 19; FIG. 15A). The strong trend for decreased methylation in infant blood DNA from cases relative to controls is further exemplified in FIG. 15B which plots the distributions of the sum of the top 19 most differentially methylated CpG loci between cases and controls, indicating significantly higher methylation in controls relative to cases (P=5.0×10⁻¹³).

Example 7

A DNA methylation based test is used for enumerating the numbers and ratios of immune cells within peripheral blood and malignant and non-malignant tissues.

Using the unique epigenetic signature of differentiated immune cells the assay allows for quantitation of immune cells by quantitative methylation specific PCR. Applications.

-   -   1. A measure of cancer susceptibility in oncology.     -   2. A measure of immune status     -   3. A measure of immunosuppression in transplantation medicine     -   4. A measure of immunosuppression in autoimmune disorders     -   5. A measure of immunosuppression within tumor tissues as a         prognostic indicator in oncology

The role of the immune system in human cancer occurrence and survival has been the subject of extensive clinical and epidemiological study. The immune system is an extraordinarily complex network of differentiated cell types, immunoglobulin, surface receptors and cytokine/chemokines factors. The central role of cell mediated immunity in tumor surveillance has been argued forcefully. Our own studies in brain tumors have pointed to atopic immune responses as being associated both with glioma occurrence and survival. Recently a specialized subset of T-cells termed T regulatory cells has been implicated in human cancer as well as a host of autoimmune and infections pathologies.

The study of cellular immune factors in cancer epidemiology both etiologic and clinical has been severely limited by need to employ cell surface markers to identify and enumerate cells in readily available specimens such as peripheral blood. The most widely accepted methods utilize fresh cells isolated from whole blood and subjected to flow cytometry using highly specific antibodies to membrane associated proteins. For example T-reg cells are sorted and counted by virtue of their expression of membrane CD4 and CD25 proteins. Many thousands of blood specimens have been archived from case control and cohort populations that are not suitable for immune cell evaluation. This patent application covers the development of epigenetic markers that will overcome these limitations and open the door to existing and future studies to utilize archival blood DNA to characterize immunologic parameters in human cancer.

Materials and Methods.

Blood Cells and Glioma Tissues

Peripheral blood cells from normal donors (granulocytes, neutrophils, monocytes, pan T cells, B cells and CD4+/CD25+ regulatory T cells) were purchased from ALLCELLS, LLC (Emeryville, Calif.) with FACScan Analysis Report attached. Fresh frozen glioma tissues were from University of California San Francisco, Brain Tumor Tissue Bank.

DNA and RNA Co-Extractions

DNA and RNA was isolated using Qiagen AllPrep Mini Kit (Qiagen, CA) according to manufacturer's protocol. Briefly, the frozen cells was quickly thawed in 37° C. water bath, washed with warm media containing 10% FBS, and then went through the protocol for cultured cells.

DNA Bisulfite Conversion

Bisulfite treatment of genomic DNA was performed using ZYMO EZ DNA Methylation Kit (Zymo Research Corp., CA) based on Zymo's instructions. About 1-2 ug of genomic DNA was used, and the reaction was incubated overnight at 50° C. Converted DNA was then column purified, and eluted twice in total of 40-60 ul buffer.

Plasmid Standard Constructs

Plasmid constructs corresponding to reported differentially methylated regions of FOXP3 gene promoter were created: transcription start site (TSS) region (region 1 [81]), and conserved region (region 2 [82]), about 4 kb down stream from region 1, 2 kb before the translation start site.

PCR products (see Table 16 for primer sequences) were generated, purified and cloned into pCR2.1-TOPO vector, using TOPO TA cloning kit (Invitrogen) according to the manufacturer's instructions and verified by sequencing. Plasmids were purified with Qiagen Plasmid Mini Kit, the concentration was determined by Nanodrop (NanoDrop ND-1000. NanoDrop Technologies, Inc. DE) and diluted to obtain final concentrations of 100, 10, 1, and 0.1 fg representing 20,000, 2,000, 200, and 20 plasmid copies as standard for quantitative PCR (qPCR) reactions.

Quantitative MSP

Real-time PCR was performed in a final reaction volume of 20 μL using ABI 7900HT Real Time PCR System. Each reaction contained 15 pmol each of methylation or non-methylation-specific forward and reverse primer (see Table 17 for primer and probe sequences), 5 pmol of hydrolysis probe, and 30 ng of bisulfite-treated genomic DNA template or a respective amount of plasmid standard. Each sample was analyzed in triplicate. Cycling conditions consisted of a 95° C. preheating step for 10 min and 50 cycles of 95° C. for 15 s followed by 1 min at 61° C.

TABLE 16 Primer sequences for plasmid standard preparation. Primer Name 5′---------3′ Size Comments FOXP3 Insert FoxSeq1F TTT ATA TTT GGT AGG GGA GAG TAG 389 bp Region 1 Bisulfite Specific FoxSeq1R ATC TCA TTA ATA CCT CTC ACC TCT  FoxSeq2F TGT TTG GGG GTA GAG GAT TTA G 336 bp Region 2 Bisulfite Specific FoxSeq2R TAT CAC CCC ACC TAA ACC AAA C FoxWT1F A TCT GGT AGG GGA GAG CAG 382 bp Region 1 Wildtype/Unmethyl FoxWT1R C TCA TTG ATA CCT CTC ACC TCT FoxWT2F T CTG GGG GTA GAG GATCCTA 332 bp Region 2 Wildtype/Unmethyl FoxWT2R TCA CCC CAC CTG GGC CAA

TABLE 17 Methylight Primer and probe sequences for quantitative MSP. Name 5′-3′ sequence Size Comments FoxReg1U5 TAG TTT GGT TTG TGG GAA ATT GTT AT 149 bp USP for region 1 FoxReg1U3 ATA ATT ATC AAC ACA CAC ACT CAT CA FoxReg1USPprobe ATC TAC AAC TTC CAC ACC ATA CAA CAT AA FoxReg1M5 GTT TGG TTT GTG GGA AAT TGT TAC 144 bp MSP for region 1 FoxReg1M3 ATT ATC AAC GCA CAC ACT CAT CG FoxReg1MSPprobe ACG ACT TCC ACA CCG TAC AAC GTA A FoxReg2U5 ATT TGG GTT TTG TTG TTA TAG TTT TTG A 108 bp USP for region 2 FoxReg2U3 CTC TTC TCT TCC TCC ATA ATA TCA FoxReg2USPprobe AAC CCA ACA CAT CCA ACC ACC ATA ACA A FoxReg2M5 TTG GGT TTT GTT GTT ATA GTT TTC GA 104 bp MSP for region 2 FoxReg2M3 CTT CTC TTC CTC CGT AAT ATC G FoxReg2MSPprobe CCG ACG CAT CCG ACC GCC ATA

Pleural Mesothelioma/Lung Adenocarcinoma Scenarios: Example 8

A 72 year old retired male shipyard worker presents with a pleural mass. The subject's DNA methylation data is obtained from cells taken from pleural fluid and the data derived by the methods described herein. This data is compared with pleural DNA methylation data obtained from Tumor Control and Normal Control pleural samples at all autosomal CpG loci by comparing the Subject DNA methylation data to a library of Tumor Control DNA methylation data and a library of Normal Control DNA methylation data (each representing same tissue of origin); and fitting by mixture modeling P(Y,C) Subject DNA methylation data to said Tumor and Normal Control DNA methylation data using recursively partitioned mixture modeling (RPMM) in conjunction with an empirical Bayes procedure generating a posterior probability distribution P(C|y*) of methylation class membership for Subject DNA y*. In this example the Subject DNA methylation data's identity with Normal Control is indicated by posterior probability of membership P(C=k|y*) at least 90% in a class k comprised of at least 95% Normal Control samples [P(control|C=k)>95%]; and establishing a metric-based criterion for comparison by computing mean methylation average beta values μ_(j) at each CpG locus j from said Normal Control DNA methylation samples data y_(ij) and fitting the distribution of squared weighted Euclidean distances d_(i) ²=Σ{(y_(ij)−μ_(j))²/[μ_(j)(1−μ_(j))]} to a gamma distribution G, and where said Subject DNA methylation data's squared weighted Euclidean distance d*²={(y_(j)*−μ_(j))²/[μ_(j)(1−μ_(j))]} is less than the 95% quantile of G it is indicated with at least 95% certainty that the subject's sample is Normal. Here the subject's squared weighted Euclidian distance d*² is greater than the 95% quantile of G indicating with at least 95% certainty that the subject's sample is cancer.

Example 9

In another example, a 70 year old man presents with chest pain and dyspnea secondary to pleural effusion. Pleural fluid is collected, spun and DNA from cell precipitate is extracted and bisulfite modified for DNA methylation profiling as in the preceding example and comparison is made to Tumor and Normal Control samples from reference tissues of origin for suspected cancer type (pleura and lung) with the method descried in the preceding example. The pleural fluid sample methylation profile indicates that the man suffers from lung adenocarcinoma.

Example 10

A 70 year old female is diagnosed with pleural mesothelioma. Prior to elective (and major) surgery to excise the tumor, a biopsy is obtained and sent for DNA methylation profiling and compared to Tumor Control samples of the same tissue origin (i.e. mesotheliomas) by applying the diagnostic steps of the preceding examples, but utilizing the Tumor Control DNA methylation sample data and not the Normal data. The subjects' prognosis is then made on the basis that it is generally equivalent to the history of subjects from which Tumor Control DNA methylation data was derived having distribution of class membership greater than about 90%. In this example, subjects with similar tumor methylation survived about 30 to 50 weeks, which is the prognosis for this subject and were refractory to cisplatin treatment.

Example 11 Non-Melanoma Squamous Cell Carcinoma of the Skin Prognosis

An individual is diagnosed with squamous cell carcinoma of the skin to be treated with surgical resection. The DNA from the resected tumor is evaluated for methylation changes as described herein. It is determined that additional therapies (chemotherapy) and enhanced screening during patient follow-up will improve patient outcome.

Example 12 Lung Cancer Example

An individual with a 30 year history of smoking is screened for early detection of cancer. Sputum samples are collected, DNA extracted followed by methylation analysis and profiles of methylation are compared as disclosed herein to a Tumor Control library of lung cancers. It is determined that presence of malignancy is probable and surgery is scheduled. At the time of surgical resection for lung cancer, the subject's surgical margins are swabbed for detection of residual disease. DNA is extracted from these surgical swabs, and methylation profiles determined. The swab sample methylation profile is compared to the resected specimen and the subject's swab sample profile is identified as having poor clinical outcome, suggesting palliative care only.

Example 13 Head and Neck Cancer

A 50 year old female has an oral cavity biopsy of an unknown mass taken and sent for DNA methylation profiling. Based on the DNA methylation profile of the tissue sample it is determined that she has oral cancer which is of a type associated with a poor prognosis.

Example 14 Bladder Cancer

A 70 year Asian male presents with pain and bleeding in his urine. A bladder mass is discovered and biopsied. DNA methylation of the mass tissue is profiled and compared to normal and tumor methylation patterns. It is determined that the tumor is invasive and the patient is assigned for aggressive therapy and enhanced screening for recurrent disease.

Example 15

A 68 year old man previously diagnosed with non-invasive stage bladder cancer and successfully removed is now undergoing screening for recurrence of the disease or progression of the disease to invasive bladder cancer. A urine sample is taken every 6 months, cells are isolated from the urine sample through centrifugation, and the DNA methylation profile is assayed and compared to a Tumor Control library from bladder tumors as well as to the patient's own, previously resected tumor profile. It is determined that the tumor has not progressed and the individual is scheduled for another screening in 6 months.

Example 16 Leukemia

A blood sample drawn from a subject at birth is sent for DNA methylation profiling and compared to a Control library of infant blood samples from individuals who are healthy and individuals who went on to develop leukemia. It is determined that the infant is at a high-risk of developing leukemia, and assigned for additional diagnostics and enhanced screening practices.

All documents referred to herein including the following publications are incorporated herein by reference in their entirety.

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SUPPLEMENTAL TABLE 1 CpG loci with differential methylation in tumor versus non-tumor pleura CpG locus Regression coefficient* Δβ** P-value Q-value Rank ADAMTS12_E52_R −1.814 0.338 0 0 1 APC_P280_R −0.940 0.040 0 0 2 APP_E8_F −0.943 0.033 0 0 3 BCAM_E100_R −0.588 0.017 0 0 4 CARD15_P302_R −1.355 0.221 0 0 5 CCND3_P435_F −0.926 0.049 0 0 6 CCNE1_P683_F −0.500 0.045 0 0 7 CSF3_E242_R 0.651 −0.057 0 0 8 CTNNA1_P382_R −0.844 0.053 0 0 9 EPHB4_E476_R −1.711 0.350 0 0 10 EPS8_E231_F −1.117 0.190 0 0 11 EPS8_P437_F −0.941 0.127 0 0 12 FANCG_E207_R −1.110 0.074 0 0 13 FER_E119_F −1.776 0.310 0 0 14 GAS1_E22_F −0.841 0.027 0 0 15 HIC1_P565_R −1.004 0.050 0 0 16 HPSE_P29_F −1.451 0.115 0 0 17 ID1_P880_F −1.106 0.147 0 0 18 IL18BP_E285_F 0.750 −0.112 0 0 19 IL8_P83_F −1.515 0.342 0 0 20 ITGA2_P26_R −0.968 0.067 0 0 21 JAG1_P66_F −1.169 0.115 0 0 22 LAMB1_E144_R −1.371 0.174 0 0 23 MCM2_P241_R −0.889 0.048 0 0 24 MCM2_P260_F −1.369 0.226 0 0 25 MLH3_P25_F −1.617 0.156 0 0 26 MUC1_P191_F −1.395 0.222 0 0 27 PCDH1_E22_F −0.857 0.037 0 0 28 PCGF4_P760_R −1.507 0.181 0 0 29 PDE1B_E141_F −0.833 0.084 0 0 30 PDGFA_P841_R −0.788 0.024 0 0 31 PRKCDBP_E206_F −0.746 0.032 0 0 32 PRKCDBP_P352_R −1.141 0.130 0 0 33 RARB_P60_F −1.635 0.246 0 0 34 RARRES1_P57_R −1.708 0.391 0 0 35 RIPK2_E123_F −0.618 0.041 0 0 36 SFN_P248_F −0.965 0.127 0 0 37 SHB_P473_R −1.239 0.037 0 0 38 SKI_E465_R −0.818 0.034 0 0 39 SMARCA3_P109_R −1.134 0.053 0 0 40 SPARC_E50_R −0.844 0.103 0 0 41 SRC_E100_R 1.325 −0.200 0 0 42 TGFA_P558_F −1.046 0.043 0 0 43 TGFB2_P632_F −0.662 0.029 0 0 44 TGFBR3_E188_R −0.855 0.031 0 0 45 TJP2_P330_R −1.404 0.066 0 0 46 TJP2_P518_F −1.815 0.266 0 0 47 TNFRSF10B_E198_R −1.145 0.082 0 0 48 TRAF4_P372_F −1.493 0.280 0 0 49 TRIP6_E33_F −0.739 0.076 0 0 50 TUBB3_P721_R −1.293 0.127 0 0 51 WNT5A_E43_F −0.951 0.063 0 0 52 YES1_P600_F −0.654 0.022 0 0 53 ACVR2B_E27_R −0.838 0.030 0 0 54 BCL3_E71_F −1.197 0.249 0 0 55 CASP8_E474_F −1.355 0.317 0 0 56 CPA4_P961_R 1.071 −0.122 0 0 57 FES_E34_R −1.187 0.109 0 0 58 GATA6_P21_R −1.435 0.127 0 0 59 ISL1_E87_R −1.869 0.363 0 0 60 ITGB4_E144_F −0.928 0.048 0 0 61 PPARD_P846_F −1.245 0.141 0 0 62 PTCH_E42_F −0.776 0.026 0 0 63 TJP1_P326_R −0.843 0.054 0 0 64 WNT2B_P1185_R −1.081 0.090 0 0 65 APP_P179_R −1.224 0.086 0 0 66 ITGB1_P451_F −1.349 0.172 0 0 67 PDGFRB_P273_F −1.205 0.276 0 0 68 IGSF4C_E65_F −1.467 0.351 0 0 69 TIMP2_P267_F −1.413 0.187 0 0 70 CDK10_E74_F −1.227 0.072 0 0 71 INHA_P1189_F −1.077 0.090 0 0 72 PHLDA2_E159_R −0.847 0.065 0 0 73 PLAU_P11_F −1.121 0.111 0 0 74 DHCR24_P406_R −1.210 0.053 0 0 75 ITGA6_P298_R −1.967 0.334 0 0 76 PDGFB_E25_R −0.823 0.161 0 0 77 ERCC1_P354_F −0.506 0.014 0 0 78 RAD54B_P227_F −1.208 0.146 0 0 79 CD9_E14_R −0.797 0.041 0 0 80 GNMT_E126_F −0.835 0.041 0 0 81 HPSE_P93_F −1.612 0.171 0 0 82 CAV1_P130_R −1.096 0.109 0 0 83 INHA_P1144_R −1.074 0.084 0 0 84 EPHB2_P165_R −1.310 0.115 0 0 85 CCR5_P630_R −0.998 0.245 0 0 86 GSTP1_seq_38_S153_R −0.811 0.032 0 0 87 DSP_P36_F −1.674 0.246 0 0 88 LIG4_P194_F −0.733 0.028 0 0 89 MYCN_E77_R −0.797 0.047 0 0 90 CDK6_P291_R −1.029 0.052 0 0 91 HOXB13_E21_F −1.727 0.330 0 0 92 IGF2R_P396_R −0.913 0.083 0 0 93 ENC1_P484_R −0.738 0.043 0 0 94 ACVR1C_P115_R −1.300 0.109 0 0 95 SMO_E57_F −0.987 0.046 0 0 96 ZMYND10_P329_F −1.304 0.245 0 0 97 EIF2AK2_E103_R −0.949 0.067 0 0 98 TGFBI_P31_R −0.651 0.064 0 0 99 CYP1B1_P212_F −1.247 0.240 0 0 100 PDGFRB_E195_R −0.744 0.072 0 0 101 P2RX7_E323_R −1.107 0.137 0 0 102 FGFR2_P460_R −1.360 0.303 0 0 103 TSG101_P257_R −1.051 0.195 0 0 104 CD34_E20_R −0.820 0.147 0 0 105 MCC_E23_R −0.764 0.053 0 0 106 PTEN_P438_F −0.540 0.015 0 0 107 NTRK3_P636_R −0.893 0.054 0 0 108 FHIT_P93_R −0.937 0.042 0 0 109 GAS1_P754_R −0.789 0.025 0 0 110 EPHB1_E202_R −1.128 0.203 0 0 111 IL1B_P829_F 1.117 −0.270 0 0 112 TIAM1_P117_F −0.935 0.046 0 0 113 IGF1R_P325_R −0.544 0.019 0 0 114 TMEFF1_E180_R −0.574 0.019 0 0 115 DAB2IP_E18_R −1.065 0.116 0 0 116 APC_E117_R −0.813 0.153 0 0 117 EXT1_E197_F −0.923 0.109 0 0 118 CTGF_E156_F −0.740 0.037 0 0 119 RARRES1_E235_F −1.146 0.060 0 0 120 CCND1_E280_R −0.978 0.062 0 0 121 PTPN6_E171_R −1.790 0.378 0 0 122 MUSK_P308_F 0.686 −0.074 0 0 123 GRB10_E85_R −0.818 0.059 0 0 124 ABL2_P459_R −1.312 0.213 0 0 125 ROR2_E112_F −0.866 0.062 0 0 126 DDIT3_P1313_R 1.353 −0.299 0 0 127 IRF5_P123_F −0.527 0.046 0 0 128 EPHB6_E342_F −1.156 0.092 0 0 129 FLT4_E206_F −1.043 0.110 0 0 130 DST_P262_R −0.859 0.046 0 0 131 FASTK_P257_F −1.062 0.126 0 0 132 PSIP1_P163_R −1.210 0.074 0 0 133 IGFBP5_E144_F −0.912 0.064 0 0 134 CASP6_P230_R −0.988 0.045 0 0 135 SLC22A2_P109_F 0.676 −0.091 0 0 136 SEMA3B_P110_R −0.783 0.091 0 0 137 PKD2_P287_R −0.721 0.043 0 0 138 TESK2_P252_R −0.455 0.014 0 0 139 ASB4_E89_F 0.574 −0.038 0 0 140 ADAMTS12_P250_R −0.795 0.027 0 0 141 ITGB4_P517_F −0.852 0.137 0 0 142 GADD45A_P737_R −0.988 0.211 0 0 143 CDH3_E100_R −1.299 0.200 0 0 144 ROR2_P317_R −1.012 0.061 0 0 145 CASP6_P201_F −0.991 0.065 0 0 146 COL6A1_P425_F −1.181 0.178 0 0 147 PSCA_P135_F 0.674 −0.105 0 0 148 S100A4_P887_R 0.643 −0.059 0 0 149 THBS1_P500_F −0.956 0.067 0 0 150 FGFR1_E317_F −0.629 0.062 0 0 151 NOTCH2_P312_R −0.417 0.009 0 0 152 XRCC2_P1077_F 0.602 −0.020 0 0 153 BMP4_P123_R −1.150 0.140 0 0 154 COPG2_P298_F 0.969 −0.049 0 0 155 SLIT2_E111_R −1.417 0.286 0 0 156 MCM6_E136_F −0.876 0.053 0 0 157 ITGA2_E120_F −0.969 0.045 0 0 158 EPHB3_E0_F −1.189 0.082 0 0 159 VEGFB_P658_F −0.814 0.033 0 0 160 FGFR2_P266_R −0.842 0.046 0 0 161 CPA4_E20_F −0.934 0.224 0 0 162 GNMT_P197_F −0.820 0.137 0 0 163 RASA1_E107_F −0.872 0.028 0 0 164 FYN_P352_R −0.809 0.049 0 0 165 PTGS1_P2_F −0.930 0.050 0 0 166 CDKN1A_E101_F −0.763 0.039 0 0 167 TGFA_P642_R −0.689 0.036 0 0 168 THPO_P585_R 0.696 −0.054 0 0 169 PTPNS1_E433_R −0.575 0.011 0 0 170 FHIT_E19_R −0.637 0.020 0 0 171 PLAUR_E123_F −0.437 0.034 0 0 172 ST6GAL1_P164_R −1.326 0.176 0 0 173 SPARC_P195_F −0.866 0.133 0 0 174 PTK7_E317_F −1.401 0.332 0 0 175 MLH3_E72_F 0.724 −0.039 0 0 176 BCAM_P205_F −1.234 0.233 0 0 177 EFNB3_P442_R −0.731 0.086 0 0 178 BCL3_P1038_R −0.345 0.012 0 0 179 SEMA3B_E96_F −0.647 0.078 0 0 180 PDGFA_P78_F −0.503 0.084 0 0 181 FLI20712_P984_R 0.650 −0.123 0 0 182 SRC_P164_F 0.450 −0.031 0 0 183 HTR1B_P107_F −1.286 0.261 0 0 184 ABCG2_P178_R −0.782 0.066 0 0 185 TNFRSF10C_P7_F 1.610 −0.379 0 0 186 FVT1_P225_F −0.778 0.054 0 0 187 KLF5_E190_R −1.055 0.070 0 0 188 HBEGF_P32_R −1.122 0.060 0 0 189 TNC_P57_F −0.772 0.054 0 0 190 MT1A_P600_F 1.071 −0.214 0 0 191 CDH1_P45_F −0.967 0.140 0 0 192 MAF_E77_R −0.943 0.083 0 0 193 GPX1_E46_R −0.485 0.014 0 0 194 PYCARD_P150_F 0.783 −0.193 0 0 195 MLH1_P381_F −0.705 0.020 0 0 196 CSF3_P309_R 0.897 −0.197 0 0 197 STK11_P295_R −0.946 0.197 0 0 198 FANCF_P13_F −0.662 0.025 0 0 199 IGFBP6_P328_R −0.829 0.088 0 0 200 IFNGR2_E164_F −0.687 0.066 0 0 201 PLXDC1_E71_F −0.737 0.068 0 0 202 PTCH2_P568_R −1.098 0.223 0 0 203 IL16_P93_R −1.185 0.284 0 0 204 WNT2B_P1195_F −0.745 0.026 0 0 205 E2F5_P516_R −0.914 0.225 0 0 206 HDAC5_E298_F −0.703 0.154 0 0 207 YES1_P216_F −1.015 0.043 0 0 208 LAMC1_P808_F −0.590 0.042 0 0 209 TRPM5_P979_F 0.832 −0.092 0 0 210 ERCC6_P698_R −1.512 0.361 0 0 211 NGFB_E353_F −1.444 0.181 0 0 212 TGFBI_P173_F −0.726 0.124 0 0 213 DAPK1_E46_R −0.591 0.096 0 0 214 WNT5A_P655_F −0.668 0.025 0 0 215 TP73_P496_F −0.827 0.043 0 0 216 DIO3_P90_F −1.264 0.288 0 0 217 CDH3_P87_R 0.736 −0.043 0 0 218 WRN_E57_F −0.685 0.072 0 0 219 INSR_E97_F −0.758 0.094 0 0 220 SFTPB_P689_R 0.530 −0.075 0 0 221 CDK2_P330_R −0.556 0.029 0 0 222 LIF_P383_R −0.842 0.185 0 0 223 GPR116_P850_F 0.477 −0.030 0 0 224 CD34_P339_R 0.688 −0.127 0 0 225 CDKN1C_P6_R −0.942 0.107 0 0 226 MLF1_P97_F −1.743 0.278 0 0 227 HLA-DOA_P191_R −1.352 0.319 0 0 228 BAX_E281_R −0.845 0.188 0 0 229 MALT1_P406_R −0.927 0.061 0 0 230 RUNX1T1_P103_F −1.237 0.237 0 0 231 DST_E31_F −0.480 0.029 0 0 232 LAMC1_E466_R −0.711 0.019 0 0 233 KLF5_P13_F −0.761 0.050 0 0 234 PLAT_P80_F −0.882 0.100 0 0 235 EPO_P162_R −1.169 0.243 0 0 236 SMAD4_P474_R −0.588 0.013 0 0 237 ALK_E183_R −0.847 0.073 0 0 238 ETS1_E253_R −0.604 0.107 0 0 239 PLAGL1_P334_F 0.855 −0.130 0 0 240 DDR1_E23_R −0.776 0.072 0 0 241 IGFBP3_E65_R 0.882 −0.070 0 0 242 LMTK2_P1034_F 0.448 −0.102 0 0 243 OAT_P465_F −1.197 0.209 0 0 244 CAV1_P169_F −0.651 0.100 0 0 245 APC_P14_F −0.789 0.114 0 0 246 TSG101_P139_R −0.528 0.032 0 0 247 IL8_E118_R −0.819 0.121 0 0 248 TCF7L2_P193_R −0.792 0.029 0 0 249 CTSH_E157_R 0.642 −0.047 0 0 250 SMARCA3_P17_R −0.891 0.071 0 0 251 COL1A1_P117_R −0.826 0.146 0 0 252 BMP3_P56_R −0.484 0.015 0 0 253 TRIP6_P1090_F −1.136 0.276 0 0 254 MGMT_P272_R −1.098 0.091 0 0 255 GAS7_E148_F −0.845 0.050 0 0 256 PKD2_P336_R −0.655 0.052 0 0 257 MMP14_P208_R −0.944 0.182 0 0 258 ICAM1_P119_R −1.114 0.073 0 0 259 COL18A1_P494_R −1.314 0.234 0 0 260 MCC_P196_R 0.601 −0.017 0 0 261 PCGF4_P92_R −0.788 0.058 0 0 262 JAG2_E54_F −0.528 0.016 0 0 263 LRP2_E20_F −0.394 0.017 0 0 264 NFKB2_P709_R −0.606 0.035 0 0 265 IL18BP_P51_R 0.854 −0.197 0 0 266 EPHB2_E297_F −0.800 0.029 0 0 267 ABCA1_P45_F −0.675 0.026 0 0 268 THY1_P20_R −1.088 0.212 0 0 269 HIC-1_seq_48_S103_R 0.656 −0.072 0 0 270 CTTN_E29_R −0.817 0.064 0 0 271 FGFR1_P204_F −0.650 0.054 0 0 272 MLF1_E243_F −1.077 0.230 0 0 273 JAG2_P264_F −0.539 0.023 0 0 274 PTPN6_P282_R −1.576 0.298 0 0 275 CDC25B_E83_F −1.303 0.086 0 0 276 CEACAM1_P44_R 0.930 −0.211 0 0 277 SEMA3F_P692_R −0.664 0.029 0 0 278 TIMP2_E394_R −0.406 0.013 0 0 279 DUSP4_P925_R −0.687 0.023 0 0 280 NEO1_P1067_F −0.784 0.080 0 0 281 SMARCB1_P220_R −0.671 0.138 0 0 282 NOTCH3_P198_R −1.192 0.275 0 0 283 IFNGR1_P307_F 0.546 −0.033 0 0 284 E2F3_P840_R −0.431 0.026 0 0 285 CASP10_P186_F −0.895 0.072 0 0 286 MCAM_P169_R −0.564 0.033 0 0 287 DAB2IP_P9_F −0.404 0.017 0 0 288 P2RX7_P597_F 0.704 −0.038 0 0 289 ABO_E110_F −0.983 0.092 0 0 290 NBL1_P24_F −0.911 0.223 0 0 291 DLL1_P386_F −0.705 0.031 0 0 292 DAPK1_P10_F −0.689 0.049 0 0 293 EPHB4_P313_R −0.565 0.044 0 0 294 CLDN4_P1120_R 0.506 −0.064 0 0 295 EPHA5_E158_R −0.828 0.039 0 0 296 ITGA6_P718_R 0.437 −0.020 0 0 297 DHCR24_P652_R −0.644 0.154 0 0 298 MTA1_P478_F −0.842 0.078 0 0 299 DDB2_P407_F −0.780 0.107 0 0 300 SMARCA4_P362_R −0.427 0.014 0 0 301 SNURF_P78_F −0.921 0.151 0 0 302 IRF7_E236_R −0.854 0.137 0 0 303 NKX3-1_P146_F −0.454 0.024 0 0 304 ABO_P312_F −0.757 0.066 0 0 305 p16_seq_47_S85_F −0.841 0.198 0 0 306 KRT13_P341_R 0.405 −0.038 0 0 307 TYK2_P494_F −0.615 0.082 0 0 308 PTPRG_P476_F −0.446 0.012 0 0 309 VAMP8_E7_F −0.810 0.200 0 0 310 FOSL2_E384_R −1.035 0.056 0 0 311 LYN_E353_F −0.570 0.079 0 0 312 VIM_P343_R −0.657 0.022 0 0 313 HLA-DOB_E432_R −0.669 0.083 0 0 314 BMP4_P199_R −0.822 0.193 0 0 315 CTSH_P238_F −0.577 0.032 0 0 316 FGF9_P862_R −0.528 0.107 0 0 317 NEU1_P745_F −0.479 0.029 0 0 318 BMPR2_P1271_F −0.549 0.033 0 0 319 TIMP3_seq_7_S38_F −0.824 0.052 0 0 320 CRIP1_P274_F −0.526 0.129 0 0 321 GRB10_P496_R 1.040 −0.251 0 0 322 NRAS_P103_R −0.532 0.020 0 0 323 IL6_E168_F −0.845 0.141 0 0 324 TFPI2_P9_F −0.523 0.023 0 0 325 SLC22A3_P634_F 0.597 −0.122 0 0 326 SMAD2_P708_R −0.335 0.011 0 0 327 PTHLH_P757_F 0.424 −0.049 0 0 328 CAPG_E228_F −0.828 0.163 0 0 329 BMPR2_E435_F 0.703 −0.028 0 0 330 CSTB_E410_F −1.071 0.061 0 0 331 ASB4_P52_R 0.759 −0.056 0 0 332 ABCA1_E120_R −0.439 0.012 0 0 333 HHIP_E94_F −0.757 0.083 0 0 334 CSK_P740_R −0.855 0.120 0 0 335 PTK2B_P673_R −0.373 0.015 0 0 336 JAK2_P772_R −0.963 0.065 0 0 337 MAP3K9_E17_R −0.844 0.054 1.00E−06 1.00E−06 338 TNFRSF10B_P108_R −0.702 0.073 1.00E−06 1.00E−06 339 WT1_P853_F −0.747 0.050 1.00E−06 1.00E−06 340 PTPRF_E178_R −0.541 0.064 1.00E−06 1.00E−06 341 S100A12_P1221_R 0.380 −0.049 1.00E−06 1.00E−06 342 CHI3L2_E10_F −0.819 0.180 1.00E−06 1.00E−06 343 FGF12_E61_R −0.606 0.074 1.00E−06 1.00E−06 344 DMP1_E194_F 0.385 −0.028 1.00E−06 1.00E−06 345 DMP1_P134_F 0.391 −0.042 1.00E−06 1.00E−06 346 TRIM29_P261_F −1.593 0.266 1.00E−06 1.00E−06 347 TNFRSF10C_E109_F 1.504 −0.316 1.00E−06 1.00E−06 348 COMT_E401_F −1.157 0.220 1.00E−06 1.00E−06 349 EPHA7_P205_R −0.652 0.045 1.00E−06 1.00E−06 350 CCND1_P343_R −0.730 0.060 1.00E−06 1.00E−06 351 PGR_P790_F 0.668 −0.132 1.00E−06 1.00E−06 352 TUBB3_P364_F −0.413 0.008 1.00E−06 1.00E−06 353 TAL1_P594_F 1.400 −0.330 1.00E−06 1.00E−06 354 HDAC11_P556_F −0.304 0.010 1.00E−06 1.00E−06 355 GABRA5_P1016_F −1.469 0.175 1.00E−06 1.00E−06 356 DAPK1_P345_R −0.650 0.034 1.00E−06 1.00E−06 357 PPP2R1B_P268_R −0.444 0.017 1.00E−06 1.00E−06 358 FAT_P279_R −0.670 0.089 1.00E−06 1.00E−06 359 PCDH1_P264_F −0.785 0.102 1.00E−06 1.00E−06 360 CHFR_P501_F −0.967 0.126 1.00E−06 1.00E−06 361 CSPG2_E38_F −1.102 0.168 2.00E−06 2.00E−06 362 AHR_P166_R −0.981 0.054 2.00E−06 2.00E−06 363 SFTPC_E13_F 0.654 −0.111 2.00E−06 2.00E−06 364 IL1RN_E42_F −1.039 0.192 2.00E−06 2.00E−06 365 FGF9_P1404_F −0.324 0.051 2.00E−06 2.00E−06 366 JAK3_P156_R 1.185 −0.287 2.00E−06 2.00E−06 367 NGFB_P13_F −0.668 0.108 2.00E−06 2.00E−06 368 BMP3_E147_F −0.911 0.115 2.00E−06 2.00E−06 369 ITK_P114_F −1.187 0.163 3.00E−06 3.00E−06 370 MAS1_P469_R 0.344 −0.020 3.00E−06 3.00E−06 371 ACVR2B_P676_F −0.594 0.056 3.00E−06 3.00E−06 372 SEMA3F_E333_R −0.514 0.060 3.00E−06 3.00E−06 373 RARB_E114_F −0.487 0.030 3.00E−06 3.00E−06 374 SNRPN_seq_12_S127_F −0.661 0.147 3.00E−06 3.00E−06 375 EFNA1_P7_F −0.334 0.008 3.00E−06 4.00E−06 376 PTHLH_E251_F 0.634 −0.137 4.00E−06 4.00E−06 377 CRIP1_P874_R −0.644 0.081 4.00E−06 4.00E−06 378 C4B_P191_F −1.041 0.107 4.00E−06 4.00E−06 379 SHH_P104_R −0.737 0.049 4.00E−06 4.00E−06 380 EDN1_E50_R 1.448 −0.081 4.00E−06 4.00E−06 381 SFTPD_E169_F 0.421 −0.046 4.00E−06 4.00E−06 382 ZMYND10_E77_R −0.604 0.061 5.00E−06 5.00E−06 383 DDR2_P743_R −1.032 0.210 5.00E−06 5.00E−06 384 SEPT9_P374_F 1.211 −0.293 5.00E−06 5.00E−06 385 EGR4_E70_F −0.680 0.154 5.00E−06 5.00E−06 386 ABL1_P53_F −0.551 0.049 5.00E−06 5.00E−06 387 GFAP_P1214_F 0.425 −0.035 5.00E−06 5.00E−06 388 WEE1_P924_R 0.608 −0.039 5.00E−06 5.00E−06 389 BIRC5_E89_F −0.900 0.041 6.00E−06 6.00E−06 390 BMPR1A_P956_F −0.438 0.017 6.00E−06 6.00E−06 391 PTPNS1_P301_R −0.527 0.016 6.00E−06 6.00E−06 392 EGFR_P260_R −0.620 0.039 6.00E−06 6.00E−06 393 CDK6_E256_F −0.338 0.041 6.00E−06 6.00E−06 394 PLXDC2_P914_R −0.693 0.059 7.00E−06 7.00E−06 395 ERG_E28_F −1.060 0.198 7.00E−06 7.00E−06 396 EPHA7_E6_F −0.632 0.035 8.00E−06 8.00E−06 397 DDR2_E331_F −1.116 0.147 8.00E−06 8.00E−06 398 LOX_P313_R −0.660 0.076 8.00E−06 8.00E−06 399 CASP3_P420_R −0.455 0.024 8.00E−06 8.00E−06 400 EPM2A_P113_F −0.610 0.070 8.00E−06 8.00E−06 401 BMP2_E48_R −0.527 0.023 9.00E−06 8.00E−06 402 EYA4_P794_F 0.866 −0.211 9.00E−06 9.00E−06 403 TNK1_P221_F −0.644 0.140 9.00E−06 9.00E−06 404 HOXA9_E252_R 1.328 −0.313 1.00E−05 9.00E−06 405 SERPINA5_P156_F 0.706 −0.174 1.00E−05 9.00E−06 406 GLI3_P453_R −0.648 0.091 1.00E−05 1.00E−05 407 TRIM29_P135_F −0.868 0.128 1.00E−05 1.00E−05 408 AREG_E25_F −0.347 0.014 1.00E−05 1.00E−05 409 GPX3_E178_F −0.556 0.074 1.10E−05 1.00E−05 410 LEFTY2_P719_F 0.416 −0.048 1.10E−05 1.10E−05 411 NTRK1_E74_F 1.424 −0.336 1.20E−05 1.10E−05 412 BCR_P422_F 0.607 −0.141 1.30E−05 1.20E−05 413 MUC1_E18_R −0.685 0.163 1.30E−05 1.20E−05 414 F2R_P88_F −0.627 0.069 1.30E−05 1.20E−05 415 CTNNA1_P185_R −0.598 0.017 1.30E−05 1.20E−05 416 GALR1_P80_F −0.802 0.047 1.40E−05 1.30E−05 417 RAD50_P191_F −0.738 0.169 1.40E−05 1.30E−05 418 ESR2_P162_F −0.948 0.141 1.40E−05 1.40E−05 419 MMP9_P237_R −0.624 0.053 1.50E−05 1.40E−05 420 MLLT3_E93_R −0.313 0.008 1.60E−05 1.50E−05 421 ETS1_P559_R −0.246 0.007 1.80E−05 1.70E−05 422 LOX_P71_F −0.534 0.029 1.90E−05 1.80E−05 423 ODC1_P424_F −0.450 0.012 2.00E−05 1.80E−05 424 PTCH2_E173_F −0.844 0.195 2.00E−05 1.90E−05 425 FLI1_E29_F −0.833 0.096 2.10E−05 1.90E−05 426 AHR_E103_F −0.244 0.007 2.10E−05 1.90E−05 427 CSF1_P217_F 0.471 −0.034 2.10E−05 1.90E−05 428 FAS_P322_R −0.506 0.038 2.10E−05 1.90E−05 429 C4B_E171_F −0.619 0.152 2.30E−05 2.10E−05 430 DAB2_P35_F −0.534 0.019 2.30E−05 2.10E−05 431 PALM2-AKAP2_P183_R −0.511 0.042 2.40E−05 2.20E−05 432 S100A2_P1186_F −0.918 0.179 2.60E−05 2.30E−05 433 EFNB3_E17_R −0.358 0.089 2.70E−05 2.40E−05 434 RARRES1_P426_R −0.677 0.165 2.70E−05 2.40E−05 435 JUNB_P1149_R −0.378 0.031 2.70E−05 2.50E−05 436 FOLR1_E368_R 0.311 −0.018 2.80E−05 2.50E−05 437 GLI2_P295_F 0.631 −0.082 2.90E−05 2.60E−05 438 MYCN_P464_R −0.519 0.016 2.90E−05 2.60E−05 439 FGF5_E16_F −0.648 0.048 3.00E−05 2.70E−05 440 NAT2_P11_F 0.506 −0.085 3.10E−05 2.70E−05 441 NDN_E131_R 0.402 −0.067 3.20E−05 2.80E−05 442 TNFSF10_E53_F 1.395 −0.320 3.20E−05 2.90E−05 443 HIC1_E151_F −0.445 0.026 3.50E−05 3.10E−05 444 APOC1_P406_R −0.401 0.052 3.70E−05 3.20E−05 445 PLAGL1_P236_R 0.494 −0.084 4.00E−05 3.50E−05 446 APBA1_E99_R 0.485 −0.034 5.20E−05 4.50E−05 447 HPN_P374_R 0.506 −0.122 5.20E−05 4.60E−05 448 HS3ST2_E145_R 1.233 −0.268 5.20E−05 4.60E−05 449 KRT13_P676_F 0.368 −0.047 5.30E−05 4.70E−05 450 IGF2AS_E4_F −0.663 0.129 5.40E−05 4.70E−05 451 GABRG3_P75_F −0.870 0.172 5.50E−05 4.80E−05 452 PEG3_E496_F 0.487 −0.119 5.80E−05 5.10E−05 453 TBX1_P520_F −0.711 0.117 6.50E−05 5.70E−05 454 RIPK3_P124_F −0.837 0.195 6.70E−05 5.80E−05 455 NQO1_E74_R −0.287 0.012 6.80E−05 5.80E−05 456 SNCG_P98_R −0.585 0.142 6.80E−05 5.90E−05 457 PROM1_P44_R −0.896 0.101 6.90E−05 5.90E−05 458 ICAM1_E242_F −0.920 0.075 7.70E−05 6.60E−05 459 PTGS1_E80_F −0.894 0.099 7.90E−05 6.80E−05 460 MYLK_E132_R −0.946 0.191 8.10E−05 7.00E−05 461 DLC1_P695_F −0.876 0.157 9.00E−05 7.70E−05 462 ALK_P28_F −0.973 0.076 9.50E−05 8.10E−05 463 ACVR1B_P572_R −0.692 0.098 9.90E−05 8.40E−05 464 COL4A3_P545_F −0.536 0.023 0.000102 8.60E−05 465 SH3BP2_E18_F −0.565 0.100 0.000103 8.70E−05 466 TRIM29_E189_F −0.876 0.154 0.000109 9.20E−05 467 IL12B_P1453_F −0.497 0.086 0.000109 9.20E−05 468 MXI1_P75_R −0.763 0.061 0.000113 9.50E−05 469 CHD2_P667_F 0.323 −0.028 0.000116 9.70E−05 470 IL1B_P582_R −0.932 0.140 0.000117 9.80E−05 471 HBII-13_E48_F −0.580 0.055 0.000118 9.80E−05 472 RRAS_P100_R −0.548 0.021 0.000132 0.00011 473 CHFR_P635_R −0.356 0.017 0.000136 0.000113 474 EGFR_E295_R −0.438 0.015 0.000136 0.000113 475 IL12B_E25_F −0.653 0.070 0.000139 0.000115 476 GLI3_E148_R 0.411 −0.026 0.000146 0.000121 477 RAB32_P493_R 0.845 −0.197 0.000155 0.000128 478 TYRO3_P366_F −0.443 0.048 0.000164 0.000135 479 TMEFF1_P626_R −0.582 0.136 0.000169 0.000139 480 SLC22A3_P528_F 0.565 −0.132 0.00017 0.000139 481 DNAJC15_P65_F −0.461 0.036 0.000172 0.000141 482 ABCC5_P444_F −0.306 0.011 0.000174 0.000142 483 EMR3_P1297_R −1.007 0.127 0.000181 0.000148 484 TNFRSF10C_P612_R −0.453 0.024 0.000184 0.000149 485 HOXA5_P1324_F 0.858 −0.188 0.00019 0.000154 486 MGMT_P281_F −0.599 0.028 0.000203 0.000164 487 NRG1_E74_F −0.452 0.031 0.000211 0.000171 488 SLC22A18_P472_R 0.411 −0.041 0.000217 0.000175 489 EFNA1_P591_R −0.262 0.009 0.000218 0.000175 490 SMO_P455_R −0.527 0.033 0.000224 0.00018 491 HRASLS_E72_R −0.687 0.034 0.000228 0.000182 492 TAL1_E122_F 1.433 −0.212 0.000228 0.000182 493 PTHR1_P258_F −0.541 0.125 0.000232 0.000185 494 MMP7_E59_F −0.519 0.112 0.00024 0.000191 495 THBS2_P605_R 0.864 −0.213 0.000241 0.000191 496 COL1A1_P5_F −0.639 0.129 0.000254 0.000202 497 DSG1_E292_F −0.388 0.035 0.000266 0.00021 498 TMPRSS4_E83_F 0.490 −0.027 0.000267 0.000211 499 GSTP1_P74_F −0.318 0.033 0.000295 0.000232 500 TSP50_E21_R 0.484 −0.070 3.00E−04 0.000236 501 ASB4_P391_F 0.434 −0.044 0.000307 0.000241 502 TP73_E155_F −0.700 0.036 0.000358 0.00028 503 LMO2_P794_R −1.057 0.183 0.000362 0.000283 504 PLA2G2A_E268_F −0.432 0.078 0.000368 0.000287 505 FAS_P65_F −0.334 0.020 0.000379 0.000295 506 CD81_P211_F 0.911 −0.203 0.00039 0.000303 507 DES_E228_R 0.863 −0.156 0.000398 0.000308 508 GABRA5_P862_R −0.978 0.122 0.000408 0.000316 509 CPA4_P1265_R −0.293 0.015 0.000416 0.000321 510 NTSR1_E109_F −0.829 0.058 0.000421 0.000325 511 DSC2_E90_F −0.588 0.121 0.000435 0.000335 512 PTGS2_P308_F −0.396 0.032 0.000446 0.000343 513 PHLDA2_P622_F −0.531 0.106 0.000457 0.00035 514 CTLA4_P1128_F −0.371 0.041 0.000475 0.000363 515 CPNE1_P138_F −0.967 0.071 0.000485 0.00037 516 NCL_P1102_F 0.459 −0.026 0.00049 0.000374 517 HOXA11_P698_F 0.947 −0.229 0.00051 0.000388 518 CDH11_P354_R −0.393 0.077 0.00052 0.000395 519 MBD2_P233_F −0.534 0.124 0.000522 0.000395 520 IGFBP7_P297_F −0.814 0.194 0.000535 0.000405 521 TCF4_P175_R −0.748 0.049 0.000538 0.000406 522 PADI4_P1011_R −0.429 0.103 0.000547 0.000412 523 S100A2_E36_R −0.587 0.134 0.000548 0.000412 524 RIPK3_P24_F −0.933 0.170 0.000561 0.000421 525 CHI3L2_P226_F −0.697 0.137 0.000566 0.000424 526 GRB10_P260_F −0.537 0.024 0.000569 0.000425 527 HIF1A_P488_F −0.456 0.029 0.000612 0.000456 528 BLK_P668_R −0.485 0.027 0.000663 0.000494 529 AXL_P223_R 0.734 −0.150 0.000666 0.000494 530 SMAD2_P848_R −0.515 0.087 0.000666 0.000494 531 FLI1_P620_R −0.579 0.046 0.000682 0.000505 532 MAS1_P657_R 0.397 −0.022 0.000721 0.000533 533 RAF1_P330_F −0.808 0.071 0.000726 0.000536 534 EMR3_E61_F −0.718 0.175 0.000759 0.000558 535 IAPP_E280_F −0.701 0.061 0.00076 0.000558 536 MAPK4_E273_R −0.534 0.093 0.000767 0.000563 537 IHH_P246_R −0.585 0.069 0.00078 0.000571 538 RIPK4_P172_F −0.591 0.057 0.000784 0.000573 539 ERBB2_P59_R 0.483 −0.020 0.000795 0.00058 540 EMR3_P39_R −0.799 0.156 0.000805 0.000586 541 EPM2A_P64_R −0.175 0.006 0.00085 0.000617 542 TUSC3_P85_R −0.652 0.069 0.000852 0.000617 543 CDKN2B_seq_50_S294_F −0.531 0.045 0.000852 0.000617 544 PPARG_E178_R −0.411 0.019 0.000856 0.000619 545 CD34_P780_R 0.410 −0.095 0.000869 0.000627 546 TES_E172_F −1.000 0.197 0.00087 0.000627 547 CDKN1B_P1161_F 1.524 −0.210 0.000872 0.000627 548 KDR_E79_F −0.421 0.027 0.000889 0.000638 549 SH3BP2_P771_R −0.501 0.079 0.000918 0.000657 550 MATK_P190_R −0.753 0.186 0.000926 0.000662 551 SEPT9_P58_R 0.741 −0.130 0.00095 0.000678 552 HOXA9_P1141_R 0.961 −0.236 0.000959 0.000682 553 MPO_P883_R −0.693 0.146 0.000959 0.000682 554 VAV2_E58_F −0.324 0.015 0.000969 0.000688 555 MAGEL2_E166_R −0.450 0.043 0.001038 0.000735 556 COL18A1_P365_R −0.546 0.043 0.001047 0.000741 557 IL1RN_P93_R −0.581 0.139 0.001054 0.000744 558 RAN_P581_R −0.554 0.127 0.001094 0.000771 559 TGFB2_E226_R −0.408 0.062 0.001131 0.000795 560 CDH11_E102_R −0.300 0.018 0.001151 0.000808 561 FRK_P258_F −0.597 0.129 0.001167 0.000818 562 DDB2_P613_R −0.564 0.084 0.001183 0.000828 563 PLAGL1_E68_R −0.676 0.114 0.001272 0.000889 564 HLA-F_E402_F −0.206 0.004 0.001276 0.00089 565 TNF_P1084_F 0.247 −0.010 0.001294 9.00E−04 566 POMC_P400_R 0.716 −0.176 0.001336 0.000928 567 LRRK1_P39_F −0.295 0.019 0.001338 0.000928 568 WNT10B_P993_F 0.859 −0.149 0.00134 0.000928 569 CCKBR_P361_R −0.577 0.021 0.001354 0.000936 570 NNAT_P544_R 0.299 −0.022 0.001374 0.000948 571 HSPA2_P162_R 0.444 −0.038 0.00139 0.000957 572 SLC22A18_P216_R 0.491 −0.074 0.001502 0.001033 573 COL6A1_P283_F −0.228 0.004 0.00152 0.001042 574 HBII-13_P991_R 0.512 −0.055 0.001521 0.001042 575 HOXB13_P17_R −0.823 0.115 0.00157 0.001074 576 CYP1B1_E83_R −0.933 0.169 0.001593 0.001088 577 EGF_E339_F −1.108 0.121 0.00164 0.001118 578 FGF7_P44_F −0.609 0.073 0.001662 0.001131 579 LCN2_P141_R −0.610 0.071 0.001707 0.001159 580 B3GALT5_E246_R −0.680 0.132 0.001747 0.001184 581 ABCB4_E429_F −0.379 0.018 0.001781 0.001205 582 ARHGAP9_P260_F 0.394 −0.034 0.001797 0.001214 583 ACTG2_P346_F 0.462 −0.080 0.001825 0.001231 584 VAMP8_P114_F −0.667 0.136 0.001844 0.001242 585 HLA-DQA2_P282_R 0.443 −0.075 0.00191 0.001284 586 LMO1_P169_F −0.329 0.012 0.001926 0.001293 587 GDF10_E39_F −0.489 0.096 0.001941 0.001301 588 CCL3_P543_R −0.636 0.070 0.00196 0.001309 589 SPI1_P929_F 0.350 −0.052 0.001961 0.001309 590 MYB_P673_R −0.648 0.058 0.001989 0.001326 591 ZIM3_P718_R −0.843 0.069 0.002 0.001331 592 TNFRSF10D_P70_F 1.178 −0.241 0.002037 0.001353 593 SNRPN_seq_18_S99_F 0.417 −0.074 0.002082 0.001381 594 HLA-DPA1_P28_R 0.725 −0.171 0.002104 0.001393 595 ASCL2_E76_R 0.793 −0.173 0.002116 0.001399 596 PDGFRA_E125_F 0.690 −0.166 0.002138 0.001411 597 FN1_P229_R 0.467 −0.043 0.002179 0.001435 598 MMP9_P189_F −0.542 0.133 0.002264 0.001489 599 PI3_P274_R −0.677 0.058 0.002291 0.001504 600 HOXC6_P585_R 0.630 −0.103 0.002619 0.001717 601 EGF_P413_F −0.684 0.082 0.002641 0.001728 602 PYCARD_P393_F −0.469 0.084 0.002654 0.001734 603 NQO1_P345_R −0.369 0.018 0.002668 0.001739 604 CTSD_P726_F −0.457 0.105 0.002671 0.001739 605 KCNQ1_P546_R 0.574 −0.110 0.0027 0.001755 606 NOTCH4_P938_F −0.567 0.098 0.002802 0.001819 607 ICAM1_P386_R −0.876 0.068 0.00294 0.001905 608 HGF_E102_R −0.685 0.121 0.00298 0.001926 609 DNAJC15_E26_R 0.547 −0.081 0.002982 0.001926 610 HDAC9_P137_R 0.820 −0.187 0.003019 0.001946 611 TEK_P479_R −0.499 0.078 0.003102 0.001996 612 SPDEF_P6_R −0.484 0.120 0.003106 0.001996 613 IGF1_E394_F −0.551 0.135 0.003147 0.002016 614 MMP3_P16_R −0.801 0.114 0.003148 0.002016 615 HOXB2_P99_F 0.535 −0.127 0.003191 0.002041 616 HPN_P823_F 0.334 −0.030 0.003232 0.002064 617 OPCML_P71_F −0.552 0.099 0.003322 0.002118 618 KRT5_E196_R −0.880 0.091 0.003333 0.002121 619 CALCA_P171_F 0.452 −0.112 0.003382 0.002146 620 TYRO3_P501_F −0.338 0.010 0.003384 0.002146 621 ALPL_P433_F 0.562 −0.131 0.003391 0.002146 622 ITPR2_P804_F −0.410 0.033 0.003394 0.002146 623 KIT_P405_F −0.681 0.062 0.003439 0.002171 624 MAP2K6_E297_F −0.592 0.042 0.003494 0.002203 625 MEG3_P235_F −0.547 0.068 0.003528 0.00222 626 SERPINA5_E69_F 0.250 −0.042 0.003585 0.002253 627 NRG1_P558_R −0.391 0.025 0.003593 0.002254 628 RET_seq_54_S260_F −0.811 0.052 0.003675 0.0023 629 ETV1_P515_F −0.590 0.055 0.003679 0.0023 630 TNFRSF10D_E27_F 1.437 −0.268 0.003818 0.002382 631 ZNF215_P71_R −0.587 0.140 0.003822 0.002382 632 ERBB4_P255_F −0.396 0.013 0.003847 0.002394 633 NOTCH1_P1198_F −0.419 0.030 0.003924 0.002438 634 DNMT3B_P352_R −0.393 0.056 0.003937 0.002442 635 ER_seq_a1_S60_F −0.605 0.067 0.003953 0.002449 636 GFAP_P56_R 0.443 −0.073 0.003977 0.00246 637 LCN2_P86_R −0.587 0.113 0.003988 0.002462 638 IL12A_E287_R −0.438 0.016 0.004044 0.002493 639 APBA1_P644_F −0.278 0.015 0.004078 0.00251 640 AGXT_P180_F −0.870 0.091 0.004106 0.002523 641 PPAT_E170_R 0.295 −0.072 0.004119 0.002528 642 CCL3_E53_R −0.630 0.134 0.00413 0.00253 643 DUSP4_E61_F −0.298 0.036 0.00457 0.002796 644 ABCG2_P310_R 1.428 −0.161 0.004666 0.00285 645 JAK3_P1075_R 0.349 −0.051 0.004692 0.002861 646 BCL6_P248_R −0.292 0.019 0.004719 0.002873 647 DLC1_P88_R 0.471 −0.094 0.004763 0.002895 648 EPHA8_P256_F −0.452 0.068 0.004783 0.0029 649 WNT2_P217_F −0.453 0.048 0.004785 0.0029 650 SOD3_P460_R −0.490 0.067 0.00486 0.002941 651 PROK2_E0_F −0.372 0.014 0.004873 0.002944 652 BSG_P211_R 1.264 −0.236 0.005046 0.003044 653 AKT1_P310_R −0.322 0.023 0.005143 0.003098 654 MFAP4_P10_R −0.442 0.094 0.00531 0.003193 655 HOXA9_P303_F 0.660 −0.129 0.005352 0.003211 656 NFKB1_P336_R −0.697 0.067 0.005355 0.003211 657 EPHX1_P1358_R 0.394 −0.082 0.005386 0.003224 658 ACVR1B_E497_R −0.510 0.019 0.005443 0.003252 659 ATP10A_P524_R −0.553 0.133 0.005448 0.003252 660 RUNX1T1_E145_R −0.507 0.113 0.005695 0.003394 661 TNFRSF1B_P167_F −0.697 0.044 0.005749 0.003421 662 GABRG3_E123_R −0.761 0.083 0.005951 0.003536 663 NBL1_E205_R −0.459 0.084 0.006052 0.003591 664 SLC5A8_P38_R 0.955 −0.169 0.006217 0.003678 665 CTSL_P264_R −0.465 0.103 0.006218 0.003678 666 UGT1A1_P564_R 0.303 −0.015 0.006251 0.003688 667 TGFB1_P833_R 0.266 −0.012 0.006261 0.003688 668 IGF2_P1036_R −0.575 0.046 0.006271 0.003688 669 HDAC9_E38_F 0.846 −0.170 0.006272 0.003688 670 PENK_P447_R 0.806 −0.149 0.00633 0.003716 671 GALR1_E52_F −0.648 0.061 0.006372 0.003735 672 INS_P804_R −0.403 0.024 0.006475 0.00379 673 DDR1_P332_R −0.592 0.135 0.006587 0.00385 674 IGF2AS_P203_F 0.637 −0.155 0.0066 0.003852 675 OGG1_E400_F −0.479 0.105 0.006635 0.003867 676 CSF2_P605_F 0.338 −0.034 0.006654 0.003872 677 IL6_P611_F −0.728 0.068 0.006764 0.00393 678 IGF2_P36_R −0.472 0.060 0.006953 0.004034 679 LRRC32_E157_F −0.314 0.016 0.007297 0.004227 680 OSM_P188_F −0.665 0.090 0.00777 0.004495 681 ITK_E166_R −0.723 0.054 0.007783 0.004496 682 MAPK12_E165_R −0.371 0.020 0.007828 0.004515 683 ABCC2_E16_R 0.803 −0.093 0.007844 0.004518 684 KRT1_P798_R 0.330 −0.051 0.007976 0.004587 685 FGF5_P238_R −0.361 0.015 0.008149 0.004679 686 TMEFF1_P234_F −0.438 0.025 0.008186 0.004694 687 UNG_P170_F −0.625 0.038 0.008373 0.004791 688 PWCR1_P357_F −0.455 0.059 0.008386 0.004791 689 MMP8_E89_R −0.369 0.029 0.008399 0.004791 690 PECAM1_P135_F 0.358 −0.057 0.008404 0.004791 691 MAF_P826_R −0.460 0.021 0.008468 0.004821 692 SEMA3C_P642_F 0.497 −0.124 0.008709 0.004951 693 KLK10_P268_R −0.306 0.036 0.009027 0.005124 694 TIAM1_P188_R −0.294 0.015 0.009098 0.005157 695 FES_P223_R −0.434 0.037 0.009708 0.005493 696 TUBB3_E91_F −0.545 0.093 0.009718 0.005493 697 RAB32_E314_R −0.373 0.024 0.009747 0.005501 698 CASP10_E139_F −0.363 0.027 0.009808 0.005527 699 PTPRH_E173_F −0.507 0.113 0.009851 0.005544 700 ERBB4_P541_F −0.390 0.014 0.009971 0.005603 701 FZD9_E458_F 0.566 −0.141 0.009993 0.005608 702 EPHA5_P66_F −0.337 0.083 0.010065 0.00564 703 PLAUR_P82_F −0.214 0.007 0.010308 0.005768 704 TDGF1_P428_R −0.360 0.090 0.010545 0.005892 705 PEG10_P978_R −0.508 0.080 0.010569 0.005897 706 HLA-DRA_P77_R −0.487 0.066 0.010923 0.006086 707 HSD17B12_E145_R −0.686 0.028 0.010999 0.00612 708 IGF1_P933_F 0.394 −0.086 0.011019 0.006122 709 CSPG2_P82_R −0.460 0.062 0.011064 0.006137 710 PTHR1_E36_R −0.303 0.017 0.011085 0.006137 711 PRSS1_P1249_R −0.450 0.093 0.011092 0.006137 712 BCL2L2_E172_F −0.386 0.022 0.011159 0.006166 713 SIN3B_P607_F −0.305 0.027 0.011611 0.006406 714 IGSF4_P454_F −0.312 0.009 0.011662 0.006421 715 MMP2_E21_R −0.521 0.039 0.01167 0.006421 716 RIPK1_P744_R 0.520 −0.060 0.011744 0.006448 717 FGF1_E5_F 0.371 −0.060 0.011753 0.006448 718 ETV6_E430_F 0.261 −0.034 0.011889 0.006514 719 FANCE_P356_R 0.947 −0.147 0.012052 0.006594 720 MMP1_P460_F −0.373 0.011 0.012646 0.00691 721 PECAM1_E32_R 0.327 −0.059 0.012808 0.006988 722 MYOD1_E156_F 0.765 −0.121 0.01301 0.007089 723 CD9_P504_F 0.683 −0.161 0.013064 0.007104 724 PALM2-AKAP2_P420_R −0.436 0.039 0.013074 0.007104 725 IGF2_E134_R −0.571 0.072 0.013222 0.007175 726 ZIM2_P22_F −0.376 0.079 0.013291 0.007202 727 WNT1_E157_F −0.590 0.071 0.013686 0.007406 728 NKX3-1_P871_R −0.261 0.010 0.013715 0.007412 729 MSH3_E3_F −0.730 0.079 0.01376 0.007425 730 MSH2_P1008_F 0.337 −0.062 0.013999 0.007544 731 MT1A_E13_R 0.847 −0.169 0.014051 0.007562 732 PRSS8_E134_R 0.344 −0.036 0.014123 0.00759 733 TFDP1_P543_R 0.223 −0.032 0.014296 0.007673 734 CSF1R_E26_F −0.467 0.033 0.014569 0.007809 735 EDN1_P39_R −0.561 0.016 0.014655 0.007834 736 PWCR1_E81_R −0.611 0.020 0.014656 0.007834 737 LTA_E28_R −0.804 0.099 0.014913 0.007961 738 SRC_P297_F 0.170 −0.006 0.014934 0.007961 739 IHH_P529_F −0.518 0.038 0.015002 0.007986 740 CDH17_E31_F 0.317 −0.021 0.015349 0.00816 741 GJB2_P791_R −0.573 0.061 0.015514 0.008237 742 ABCB4_P51_F −0.283 0.014 0.015945 0.008454 743 THBS1_E207_R 1.165 −0.099 0.016173 0.008564 744 PDE1B_P263_R −0.630 0.031 0.016375 0.008659 745 GPX1_P194_F −0.476 0.041 0.016466 0.008695 746 CSF1_P339_F −0.206 0.006 0.016595 0.008752 747 DNMT2_P199_F 0.260 −0.033 0.016828 0.008862 748 TGFB3_E58_R −0.584 0.110 0.016861 0.008868 749 MT1A_P49_R 1.260 −0.161 0.016896 0.008875 750 NR2F6_E375_R −0.142 0.011 0.016929 0.00888 751 IL4_P262_R −0.195 0.023 0.017192 0.009006 752 TFPI2_P152_R −0.177 0.020 0.017236 0.009012 753 FABP3_P598_F −0.438 0.048 0.017249 0.009012 754 SPI1_E205_F 0.224 −0.055 0.01728 0.009016 755 FGFR4_P610_F 0.255 −0.026 0.017413 0.009074 756 HIC2_P498_F 0.719 −0.073 0.017529 0.009122 757 MMP19_P306_F −0.392 0.056 0.017897 0.009301 758 IFNG_P188_F −0.474 0.062 0.018057 0.009372 759 TNFRSF10A_P91_F −0.646 0.094 0.018751 0.00972 760 HHIP_P307_R −0.584 0.061 0.019229 0.009954 761 KRAS_E82_F −0.282 0.064 0.019631 0.010149 762 GSTM2_E153_F 0.857 −0.163 0.019677 0.010159 763 ERCC3_P1210_R −0.282 0.021 0.020003 0.010307 764 CDKN2A_E121_R −0.302 0.019 0.020016 0.010307 765 SFN_E118_F −0.521 0.053 0.02017 0.010373 766 SOX17_P303_F 0.648 −0.150 0.020251 0.010401 767 CD86_P3_F −0.627 0.130 0.020595 0.010564 768 AREG_P217_R −0.239 0.034 0.020741 0.010625 769 AATK_E63_R −0.449 0.028 0.021087 0.010789 770 SIN3B_P514_R −0.564 0.050 0.021142 0.010803 771 TMEFF2_P210_R −0.516 0.089 0.02142 0.01093 772 SHB_P691_R −0.569 0.047 0.021477 0.010945 773 WNT10B_P823_R 0.579 −0.130 0.021649 0.011019 774 RBL2_P250_R −0.385 0.027 0.021702 0.011031 775 MYCL1_P502_R −0.447 0.037 0.021919 0.011128 776 TNFRSF1B_E5_F −0.248 0.026 0.021974 0.011141 777 CD81_P272_R 0.359 −0.070 0.022429 0.011357 778 PLXDC1_P236_F −0.479 0.023 0.022671 0.011465 779 HCK_P858_F 0.492 −0.120 0.02286 0.011546 780 SOX1_P294_F 0.872 −0.114 0.023098 0.011651 781 MMP7_P613_F 0.150 −0.018 0.023319 0.011747 782 LEFTY2_P561_F 0.312 −0.078 0.023379 0.011763 783 FGF6_P139_R 0.311 −0.026 0.023912 0.012001 784 MAP2K6_P297_R −0.309 0.040 0.023914 0.012001 785 APBA2_P305_R −0.316 0.030 0.024019 0.012038 786 RUNX3_E27_R −0.538 0.068 0.024418 0.012223 787 SLC14A1_E295_F −0.388 0.050 0.024774 0.012385 788 SEMA3A_P343_F −0.394 0.042 0.02524 0.012602 789 HOXC6_P456_R 0.548 −0.087 0.025293 0.012613 790 MOS_E60_R 0.720 −0.158 0.025721 0.01281 791 LMO1_E265_R −0.406 0.048 0.025964 0.012914 792 HOXA11_E35_F 0.669 −0.137 0.02643 0.01313 793 DES_P1006_R −0.342 0.053 0.026518 0.013157 794 SLC5A5_E60_F 0.393 −0.072 0.026586 0.013167 795 ASCL2_P360_F 0.621 −0.132 0.026604 0.013167 796 USP29_P205_R 0.198 −0.022 0.026979 0.013335 797 CCNA1_P216_F −0.654 0.059 0.027392 0.013523 798 LRRK1_P834_F −0.279 0.059 0.027561 0.013589 799 TJP1_P390_F −0.332 0.013 0.02764 0.013611 800 TIMP3_P690_R 0.176 −0.007 0.027838 0.013691 801 ERN1_P809_R 0.501 −0.125 0.02796 0.013734 802 MMP2_P303_R 0.742 −0.136 0.02849 0.013977 803 TPEF_seq_44_S36_F −0.354 0.016 0.028727 0.014075 804 CDH1_P52_R −0.437 0.042 0.029493 0.014433 805 SLC22A2_E271_R 0.184 −0.007 0.029882 0.014606 806 OSM_P34_F −0.442 0.092 0.029956 0.014623 807 WNT8B_E487_F 0.253 −0.032 0.030208 0.014728 808 MST1R_E42_R −0.410 0.102 0.030858 0.015027 809 PTPRG_E40_R −0.201 0.012 0.031117 0.015134 810 FN1_E469_F 0.864 −0.084 0.031651 0.015374 811 COL1A2_P48_R 0.979 −0.157 0.032437 0.015737 812 SEMA3C_E49_R −0.337 0.024 0.032568 0.015781 813 UGT1A7_P751_R −0.214 0.006 0.032646 0.015799 814 SERPINE1_E189_R −0.283 0.049 0.032937 0.015921 815 IL17RB_P788_R −0.481 0.023 0.033167 0.016012 816 MAPK14_P327_R −0.379 0.060 0.033957 0.016373 817 GJB2_P931_R 0.440 −0.110 0.034011 0.016379 818 NFKB1_P496_F −0.247 0.038 0.034165 0.016434 819 CDKN2B_E220_F −0.254 0.017 0.034666 0.016654 820 GNG7_P903_F 0.146 −0.012 0.035472 0.017004 821 DIRAS3_E55_R −0.325 0.030 0.03548 0.017004 822 CEACAM1_E57_R 0.664 −0.112 0.036093 0.017257 823 MMP9_E88_R −0.336 0.029 0.036096 0.017257 824 IL10_P85_F −0.384 0.073 0.036347 0.017356 825 POMC_E254_F −0.465 0.037 0.036853 0.017556 826 RARA_E128_R −0.350 0.038 0.036854 0.017556 827 CXCL9_E268_R −0.353 0.046 0.037344 0.017767 828 ZIM3_E203_F −0.374 0.013 0.037495 0.017818 829 EIF2AK2_P313_F 1.011 −0.102 0.039147 0.018581 830 CDH11_P203_R −0.341 0.015 0.039445 0.01869 831 TFAP2C_P765_F −0.684 0.067 0.039473 0.01869 832 MDS1_E45_F 0.310 −0.018 0.03962 0.018737 833 GJB2_E43_F −0.421 0.027 0.039939 0.018865 834 PAX6_P1121_F 0.591 −0.059 0.040216 0.018974 835 EDNRB_P709_R −0.333 0.014 0.04071 0.019164 836 FZD9_P15_R −0.515 0.035 0.040718 0.019164 837 TAL1_P817_F 0.374 −0.080 0.042726 0.020086 838 CD40_P372_R 0.615 −0.134 0.042778 0.020086 839 SPDEF_E116_R 0.313 −0.077 0.044138 0.020668 840 NOS3_P38_F −0.357 0.053 0.04415 0.020668 841 FZD9_P175_F −0.482 0.105 0.044175 0.020668 842 ESR2_E66_F −0.716 0.059 0.04446 0.020777 843 HTR2A_P853_F −0.531 0.045 0.044674 0.020852 844 MCAM_P265_R −0.304 0.053 0.044861 0.020915 845 IPF1_P750_F 0.461 −0.110 0.045301 0.021095 846 MC2R_E455_F −0.652 0.051 0.045565 0.021193 847 DCC_E53_R 0.376 −0.092 0.04598 0.021353 848 NEFL_P209_R 0.500 −0.099 0.046018 0.021353 849 NTRK2_P395_R −0.594 0.039 0.046298 0.021434 850 DSP_P440_R 0.650 −0.033 0.046303 0.021434 851 SERPINB5_P19_R −0.713 0.057 0.046667 0.021578 852 MAD2L1_E93_F 0.187 −0.033 0.047288 0.021839 853 CD40_E58_R 0.815 −0.098 0.047981 0.022133 854 TFF2_P178_F −0.372 0.059 0.048165 0.022192 855 EPHA3_E156_R −0.441 0.035 0.04835 0.022251 856 FRK_P36_F −0.356 0.086 0.049007 0.022527 857 LTB4R_P163_F 0.210 −0.024 0.050568 0.023202 858 EPHA2_P340_R −0.267 0.052 0.050593 0.023202 859 FGFR3_P1152_R −0.385 0.095 0.050794 0.023267 860 GP1BB_E23_F −0.480 0.086 0.051543 0.023583 861 HRASLS_P353_R 0.294 −0.072 0.051962 0.023747 862 LTB4R_E64_R 0.267 −0.038 0.052575 0.023999 863 MET_E333_F −0.305 0.057 0.053256 0.024282 864 RUNX3_P247_F −0.505 0.076 0.053831 0.024516 865 TFF2_P557_R −0.381 0.019 0.054146 0.024631 866 TNC_P198_F −0.232 0.030 0.05488 0.024936 867 GUCY2D_P48_R −0.414 0.071 0.055703 0.025281 868 ALOX12_P223_R −0.470 0.109 0.056236 0.025493 869 UGT1A1_E11_F −0.156 0.004 0.056522 0.025594 870 TFF1_P180_R −0.290 0.044 0.056598 0.025599 871 DSC2_P407_R −0.194 0.012 0.056877 0.025695 872 CFTR_P372_R −0.427 0.100 0.058061 0.0262 873 NTRK3_P752_F −0.245 0.010 0.05815 0.02621 874 TFAP2C_E260_F 0.269 −0.016 0.058225 0.026211 875 NPY_E31_R −0.431 0.103 0.058283 0.026211 876 APOA1_P75_F −0.530 0.070 0.05848 0.026269 877 CYP2E1_P416_F −0.540 0.039 0.058814 0.026389 878 SNURF_E256_R −0.246 0.036 0.059449 0.026643 879 NGFR_E328_F −0.460 0.055 0.060121 0.026887 880 GPATC3_P410_R −0.489 0.075 0.060129 0.026887 881 NOTCH1_E452_R 0.168 −0.007 0.060549 0.027044 882 ERBB3_E331_F −0.420 0.042 0.061126 0.027271 883 NOTCH4_E4_F 0.467 −0.116 0.061305 0.02732 884 MLLT6_P957_F −0.505 0.050 0.061746 0.027485 885 NGFR_P355_F 0.403 −0.097 0.061901 0.027523 886 ZP3_E90_F 0.931 −0.097 0.063114 0.028031 887 APBA2_P227_F −0.274 0.017 0.063607 0.028218 888 IFNGR2_P377_R −0.388 0.096 0.063763 0.028256 889 ISL1_P379_F −0.524 0.051 0.063877 0.028274 890 SGCE_E149_F −0.466 0.054 0.064076 0.02833 891 ISL1_P554_F −0.509 0.069 0.06416 0.028336 892 GABRB3_E42_F −0.488 0.055 0.064369 0.028396 893 FLT1_E444_F −0.341 0.015 0.065339 0.028792 894 H19_P1411_R 0.228 −0.029 0.065614 0.028881 895 EVI1_E47_R 0.731 −0.122 0.066825 0.029381 896 PTCH2_P37_F −0.159 0.011 0.066912 0.029387 897 SYK_E372_F 0.699 −0.050 0.070817 0.031067 898 ZP3_P220_F −0.348 0.046 0.071584 0.031368 899 EGF_P242_R −0.315 0.038 0.071805 0.03143 900 LTA_P214_R −0.301 0.028 0.072635 0.031758 901 TCF4_P317_F 0.556 −0.067 0.073168 0.031956 902 CSF1R_P73_F −0.227 0.056 0.073518 0.032073 903 COL1A2_P407_R 0.376 −0.092 0.073886 0.032198 904 JAK3_E64_F 0.658 −0.100 0.074311 0.032347 905 GAS7_P622_R 0.378 −0.082 0.075309 0.032746 906 EDNRB_P148_R −0.319 0.014 0.076191 0.033093 907 SNCG_P53_F −0.329 0.082 0.076311 0.033108 908 FLT1_P615_R 0.772 −0.103 0.076508 0.033157 909 INS_P248_F −0.254 0.028 0.077583 0.033586 910 GML_E144_F 0.494 −0.060 0.079366 0.03432 911 SCGB3A1_E55_R 0.548 −0.104 0.080353 0.034709 912 APOC2_P377_F −0.211 0.032 0.080858 0.034889 913 HTR1B_E232_R 0.488 −0.103 0.081073 0.034927 914 MYBL2_P354_F −0.509 0.075 0.081123 0.034927 915 EPHA3_P106_R −0.504 0.064 0.081474 0.035039 916 FGF8_E183_F −0.444 0.024 0.082005 0.035229 917 SFRP1_P157_F −0.613 0.050 0.085171 0.03655 918 GNAS_E58_F −0.188 0.021 0.085517 0.036658 919 DBC1_P351_R 0.590 −0.079 0.085707 0.0367 920 NPR2_P1093_F −0.282 0.038 0.085826 0.036711 921 MKRN3_E144_F −0.478 0.035 0.086212 0.036836 922 WT1_E32_F −0.300 0.015 0.087346 0.03728 923 TMPRSS4_P552_F 0.270 −0.023 0.088315 0.037653 924 CHGA_P243_F −0.300 0.065 0.088782 0.037811 925 HS3ST2_P546_F −0.348 0.069 0.089142 0.037913 926 RIPK4_E166_F −0.296 0.020 0.089213 0.037913 927 EPHA1_E46_R −0.377 0.021 0.090715 0.03851 928 NTRK2_P10_F −0.447 0.021 0.090851 0.038526 929 SNURF_P2_R 0.175 −0.043 0.092269 0.039085 930 DSG1_P159_R −0.206 0.021 0.092761 0.039251 931 CHGA_E52_F 0.522 −0.101 0.093864 0.039673 932 FGF1_P357_R −0.375 0.063 0.093959 0.039673 933 HLA-DRA_P132_R 0.457 −0.044 0.094128 0.039702 934 PROK2_P390_F 0.951 −0.080 0.094401 0.039774 935 CCNC_P132_R −0.408 0.013 0.096541 0.040632 936 PARP1_P610_R 0.272 −0.038 0.097318 0.04087 937 HOXA5_E187_F −0.350 0.069 0.097339 0.04087 938 DBC1_E204_F −0.284 0.047 0.097416 0.04087 939 EPO_E244_R 0.702 −0.102 0.101289 0.042449 940 GSTM1_P266_F 0.327 −0.081 0.105957 0.044318 941 SLIT2_P208_F −0.317 0.031 0.105974 0.044318 942 RASSF1_P244_F 1.017 −0.070 0.106421 0.044458 943 ZNFN1A1_P179_F −0.246 0.007 0.107221 0.044745 944 TK1_P62_R −0.627 0.020 0.107905 0.044944 945 IL6_P213_R −0.344 0.036 0.107927 0.044944 946 ESR1_P151_R 0.487 −0.110 0.108424 0.045104 947 MOS_P27_R 0.486 −0.043 0.108953 0.045276 948 GNG7_E310_R 0.138 −0.004 0.109796 0.045578 949 PPARG_P693_F 0.213 −0.034 0.110297 0.045738 950 NID1_P677_F −0.389 0.033 0.110847 0.045917 951 ROR1_P6_F −0.138 0.007 0.110966 0.045918 952 GSTM2_P109_R 0.601 −0.078 0.111643 0.04615 953 BMPR1A_E88_F −0.134 0.024 0.112336 0.046388 954 BCR_P346_F 0.274 −0.061 0.112923 0.046582 955 NEFL_E23_R −0.388 0.078 0.113224 0.046648 956 LRRC32_P865_R −0.415 0.018 0.113378 0.046648 957 FANCA_P1006_R 0.115 −0.013 0.11344 0.046648 958 TRIP6_P1274_R −0.294 0.073 0.115795 0.047567 959 PLXDC2_E337_F −0.311 0.013 0.116116 0.047622 960 PRDM2_P1340_R −0.145 0.009 0.11617 0.047622 961 IL13_E75_R −0.151 0.007 0.117271 0.047971 962 USP29_E274_F 0.257 −0.016 0.117359 0.047971 963 TDG_E129_F −0.136 0.020 0.117387 0.047971 964 IGFBP2_P306_F 0.543 −0.075 0.117787 0.048085 965 TMEFF2_E94_R −0.175 0.020 0.119139 0.048586 966 SPP1_P647_F −0.305 0.053 0.119587 0.048718 967 PSCA_E359_F −0.285 0.064 0.120323 0.048967 968 COL1A2_E299_F 0.680 −0.104 0.122839 0.04994 969 *Negative coefficient indicates decreased methylation in tumor relative to non-tumor pleur; **Delta average beta non-tumor pleura less tumor

SUPPLEMENTAL TABLE 2 Locus-by-locus analysis of CpG methyaltion in tumors from asbestos exposed versus unexposed mesothelioma patients Regression Label coefficient* P-value Q-value RANK CASP10_E139_F 0.232 0.000 0.011 1 TDGF1_P428_R 0.190 0.000 0.038 2 DES_E228_R 0.254 0.000 0.038 3 BSG_P211_R 0.449 0.000 0.061 4 GP1BB_P278_R 0.276 0.000 0.064 5 FZD9_E458_F 0.276 0.000 0.064 6 SHB_P691_R 0.284 0.001 0.072 7 ASCL2_P609_R 0.266 0.001 0.072 8 PAX6_P50_R 0.408 0.001 0.077 9 GP1BB_E23_F 0.291 0.001 0.086 10 IGF2AS_E4_F 0.217 0.001 0.086 11 CD40_P372_R 0.306 0.001 0.104 12 ALOX12_E85_R 0.271 0.002 0.104 13 ASCL2_P360_F 0.257 0.002 0.104 14 ALOX12_P223_R 0.251 0.002 0.104 15 ID1_P659_R 0.092 0.002 0.104 16 HOXA9_E252_R 0.290 0.002 0.104 17 DLC1_E276_F 0.251 0.002 0.108 18 PTPN6_P282_R 0.195 0.002 0.108 19 IRF5_E101_F 0.166 0.002 0.117 20 AATK_P519_R 0.167 0.003 0.132 21 VAMP8_E7_F 0.154 0.003 0.132 22 EPO_E244_R 0.360 0.003 0.132 23 CHGA_E52_F 0.278 0.003 0.132 24 PENK_E26_F 0.233 0.003 0.132 25 TAL1_E122_F 0.255 0.003 0.132 26 JAK3_E64_F 0.313 0.004 0.133 27 IGF2AS_P203_F 0.218 0.004 0.137 28 TAL1_P817_F 0.183 0.005 0.161 29 HOXA11_P698_F 0.238 0.005 0.161 30 CDKN1C_P626_F 0.273 0.005 0.161 31 EPM2A_P64_R 0.048 0.006 0.175 32 VAMP8_P114_F 0.215 0.006 0.175 33 HOXB2_P99_F 0.178 0.006 0.175 34 PAX6_P1121_F 0.214 0.006 0.175 35 PYCARD_P150_F 0.117 0.007 0.179 36 SLC5A8_P38_R 0.259 0.007 0.179 37 ASCL2_E76_R 0.200 0.007 0.179 38 ABL1_P53_F 0.133 0.007 0.179 39 CD81_P272_R 0.158 0.007 0.179 40 PAX6_E129_F 0.332 0.007 0.179 41 TAL1_P594_F 0.242 0.008 0.199 42 NOS3_P38_F 0.138 0.009 0.200 43 SLC5A8_E60_R 0.206 0.009 0.200 44 SOX17_P303_F 0.237 0.010 0.200 45 DIO3_E230_R 0.152 0.010 0.200 46 TNFSF10_P2_R 0.304 0.010 0.200 47 HOXA11_E35_F 0.237 0.010 0.200 48 ZIM2_P22_F 0.128 0.010 0.200 49 AATK_P709_R 0.173 0.010 0.200 50 SEMA3F_P692_R 0.114 0.010 0.200 51 HS3ST2_E145_R 0.213 0.011 0.200 52 MYBL2_P354_F 0.290 0.011 0.200 53 CYP1B1_E83_R 0.292 0.011 0.200 54 LMO2_E148_F 0.159 0.011 0.200 55 E2F3_P840_R 0.079 0.011 0.200 56 CDKN2A_E121_R 0.130 0.011 0.200 57 SOX17_P287_R 0.210 0.012 0.200 58 SOX1_P1018_R 0.296 0.012 0.200 59 SCGB3A1_E55_R 0.234 0.012 0.204 60 MYLK_E132_R 0.230 0.013 0.215 61 SFTPB_P689_R −0.074 0.013 0.215 62 ASCL1_P747_F 0.176 0.014 0.215 63 MEST_P4_F 0.241 0.014 0.215 64 IRAK3_P185_F 0.265 0.015 0.225 65 MT1A_E13_R 0.248 0.015 0.225 66 CCL3_E53_R 0.163 0.016 0.237 67 ZNFN1A1_E102_F 0.126 0.016 0.237 68 CD81_P211_F 0.182 0.016 0.237 69 CSK_P740_R 0.169 0.017 0.237 70 MAPK12_E165_R 0.132 0.017 0.237 71 LIMK1_P709_R 0.170 0.017 0.237 72 CDKN2B_E220_F 0.112 0.018 0.241 73 TIMP3_P690_R −0.059 0.018 0.241 74 MMP9_P189_F 0.127 0.018 0.243 75 TSP50_P137_F 0.196 0.019 0.243 76 CHI3L2_P226_F 0.135 0.019 0.243 77 MBD2_P233_F 0.102 0.019 0.243 78 THY1_P20_R 0.191 0.019 0.246 79 ACVR1_E328_R −0.193 0.020 0.255 80 EPO_P162_R 0.189 0.021 0.257 81 APOC1_P406_R 0.072 0.021 0.259 82 MYBL2_P211_F 0.374 0.022 0.262 83 MSH3_E3_F 0.174 0.023 0.269 84 CD40_E58_R 0.236 0.023 0.274 85 JAK3_P156_R 0.199 0.024 0.274 86 EPHB6_P827_R −0.055 0.025 0.280 87 CASP10_P186_F 0.170 0.025 0.280 88 TYRO3_P366_F 0.093 0.025 0.280 89 ZIM2_E110_F 0.102 0.026 0.290 90 RASSF1_E116_F 0.364 0.027 0.291 91 EFNB3_E17_R 0.068 0.027 0.291 92 MYH11_P236_R −0.269 0.027 0.291 93 ZNF215_P129_R 0.275 0.027 0.291 94 PARP1_P610_R 0.128 0.028 0.291 95 IGF2_P1036_R 0.188 0.028 0.296 96 CRIP1_P874_R 0.110 0.029 0.297 97 ETS2_P684_F 0.294 0.029 0.297 98 NPY_P295_F 0.227 0.031 0.317 99 HLA-DPB1_E2_R −0.158 0.032 0.317 100 TNFSF10_E53_F 0.216 0.032 0.317 101 IRF5_P123_F 0.063 0.032 0.317 102 IGFBP7_P297_F 0.194 0.033 0.317 103 TFF1_P180_R 0.094 0.033 0.317 104 GUCY2D_E419_R 0.283 0.034 0.318 105 TNFRSF10C_E109_F 0.168 0.034 0.318 106 FZD9_P175_F 0.187 0.034 0.319 107 CASP2_P192_F 0.244 0.035 0.320 108 ASB4_P52_R −0.081 0.035 0.320 109 MT1A_P49_R 0.249 0.036 0.324 110 *Positive coefficient indicates increased methylation in asbestos exposed individuals

SUPPLEMENTAL TABLE 3 Top CpG loci for discriminating RPMM classes, (lung adenocarcinoma, mesothelioma, non-tumor lung, and non-tumor pleura) GENE CpG AUC Value RARRES1 P57 1.000 MLH3 P25 1.000 ITGA6 P298 0.999 IGSF4C E65 0.999 DSP P36 0.999 TRAF4 P372 0.998 INHA P1144 0.998 BCL3 E71 0.998 MLF1 P97 0.998 LAMB1 E144 0.997 CDK10 E74 0.997 ITGB1 P451 0.997 FER E119 0.997 ADAMTS12 E52 0.996 ABL2 P459 0.996 NGFB E353 0.996 GATA6 P21 0.996 ACVR1C P115 0.996 HPSE P93 0.996 EPHB4 E476 0.995 DHCR24 P406 0.995 JAG1 P66 0.995 HPSE P29 0.994 PTCH E42 0.994 TGFA P558 0.994 EPS8 E231 0.994 MCM2 P260 0.994 COL6A1 P425 0.993 EPHB3 E0 0.993 ENC1 P484 0.993 APP E8 0.992 INHA P1189 0.992 APP P179 0.992 TIMP2 P267 0.991 CCND1 E280 0.991 GSTP1 seq 0.991 SLIT2 E111 0.991 FGFR2 P460 0.991 LIG4 P194 0.990 PHLDA2 E159 0.990 BCAM P205 0.990 CYP1B1 P212 0.989 TSG101 P257 0.988 THBS1 P500 0.988 TUBB3 P721 0.988 CAV1 P130 0.987 PLAU P11 0.987 FHIT E19 0.986 GNMT E126 0.986 PSIP1 P163 0.986

SUPPLEMENTAL TABLE 4 Top sample type discriminatory CpG loci from random forests analysis, all samples (lung adenocarcinoma, mesothelioma, non-tumor lung, and non-tumor pleura). GENE CpG % Inc MSE* TNFSF10 P2 33.0 CEACAM1 P44 31.9 DDR2 E331 29.4 RARRES1 P57 29.4 TNFSF10 E53 28.5 TJP2 P518 27.6 TNFRSF10C P7 27.4 CLDN4 P1120 26.8 BSG P211 26.7 PRKCDBP P352 26.2 TNFRSF10C E109 26.0 TJP2 P330 25.7 WNT10B P993 25.5 IGF2R P396 24.2 XRCC2 P1077 24.1 HDAC1 P414 24.0 SRC E100 24.0 DDIT3 P1313 23.6 FLJ20712 P984 22.7 ERBB2 P59 21.0 CSF3 E242 20.8 CSF3 P309 20.5 TMPRSS4 E83 19.9 PSCA P135 19.8 SPARC P195 19.7 SRC P164 19.7 IGSF4C E65 18.7 IFNGR1 P307 18.7 HCK P858 18.6 ERN1 P809 18.5 SPARC E50 18.0 SFTPB P689 17.9 COPG2 P298 17.9 PLA2G2A P528 17.7 HPSE P93 17.7 CSF2 P605 17.4 HLA-DPA1 P28 17.3 KIAA1804 P689 17.2 EYA4 P794 17.1 FGF2 P229 17.1 HTR1B P107 16.8 ZNF215 P71 16.8 IL18BP E285 16.7 SLC22A18 P216 16.5 SHB P473 16.5 WT1 P853 16.4 MAP3K1 P7 16.0 MAS1 P469 16.0 ID1 P880 15.9 IL1B P582 15.7 *MSE is computed on the out-of-bag data for each tree and computed again after permuting sample type, differences are

SUPPLEMENTAL TABLE 5 Top CpG loci for discriminating RPMM classes, lung adenocarcinoma versus mesothelioma GENE CpG AUC Value ITGA6 P298 1.000 CDK10 E74 0.998 HTR1B P107 0.997 PTCH E42 0.997 INHA P1144 0.997 LAMB1 E144 0.995 IGF2R P396 0.995 RARRES1 P57 0.995 IGSF4C E65 0.994 APP P179 0.994 PCDH1 E22 0.994 MLH3 P25 0.994 ENC1 P484 0.994 SLIT2 E111 0.993 RARB P60 0.992 NGFB E353 0.992 MLF1 P97 0.992 DSP P36 0.992 ADAMTS12 E52 0.992 GATA6 P21 0.992 GSTP1 S153 0.992 TGFA P558 0.992 DHCR24 P406 0.991 BCAM P205 0.991 HPSE P29 0.990 ITGB1 P451 0.990 CPA4 P961 0.990 APP E8 0.989 WNT2B P1185 0.989 TGFB2 P632 0.988 INHA P1189 0.988 LIG4 P194 0.988 ABL2 P459 0.987 EPHB4 E476 0.986 COL18A1 P494 0.985 ABO E110 0.985 GNMT E126 0.984 FHIT E19 0.984 EPS8 E231 0.984 TRAF4 P372 0.984 SHB P473 0.983 EPHB3 E0 0.983 BCL3 E71 0.982 CYP1B1 P212 0.980 PLAU P11 0.980 TNFRSF10B E198 0.980 HPSE P93 0.980 JAG1 P66 0.979 ACVR1C P115 0.978 KLF5 E190 0.978

SUPPLEMENTAL TABLE 6 Top sample type discriminatory CpG loci from random forests analysis, lung adenocarcinoma and mesothelioma GENE CpG % Inc MSE* CLDN4 P1120 33.7 TJP2 P518 31.7 TMPRSS4 E83 30.3 DDR2 E331 29.7 SPARC P195 29.3 DDIT3 P1313 28.4 SFTPB P689 28.3 CEACAM1 P44 27.5 TNFRSF10C P7 27.1 WEE1 P924 26.9 SRC E100 26.3 XRCC2 P1077 25.5 TNFRSF10C E109 25.3 SRC P164 25.2 BSG P211 24.7 PSCA P135 23.6 CSF3 P309 23.5 WT1 E32 22.7 TJP2 P330 21.9 WT1 P853 21.5 FGF2 P229 21.3 IGF2R P396 21.0 SPARC E50 20.3 TNFSF10 E53 19.6 FLJ20712 P984 19.0 TNFSF10 P2 18.9 SPDEF E116 17.8 PTCH E42 17.4 MAS1 P469 17.1 HTR1B P107 16.7 HGF P1293 16.6 MT1A P600 16.6 HTR1B P222 16.2 HIC-1 S103 16.2 EPHA5 E158 16.2 TMPRSS4 P552 16.1 ASB4 E89 16.0 PAX6 P1121 16.0 FES E34 15.7 CDK10 E74 15.3 CSF2 P605 15.3 GNMT E126 15.2 TGFBI P173 15.1 ABO E110 14.9 PRKCDBP P352 14.8 CPA4 P961 14.6 SMO E57 14.6 HPSE P29 14.6 DHCR24 P406 14.6 PLAT P80 14.5 *MSE is computed on the out-of-bag data for each tree and computed again after permuting sample type, differences are

SUPPLEMENTAL TABLE 7 CpG loci with differential methylation between lung adenocarcinoma and mesothelioma (Q - value ranked) Higher methylation in: lung adenocarcinoma, mesothelioma Regression GENE_CpG coefficient P-value Q-value Rank ABL2_P459_R −1.23 0 0 1 ABO_E110_F −1.11 0 0 2 ABO_P312_F −0.87 0 0 3 ACVR2B_E27_R −0.65 0 0 4 ADAMTS12_E52_R −1.74 0 0 5 ADAMTS12_P250_R −1.40 0 0 6 AGTR1_P154_F −1.83 0 0 7 AGTR1_P41_F −1.92 0 0 8 AIM2_P624_F 0.98 0 0 9 ALK_E183_R −0.81 0 0 10 APC_E117_R −1.40 0 0 11 APC_P14_F −1.51 0 0 12 APC_P280_R −1.76 0 0 13 APP_E8_F −0.84 0 0 14 APP_P179_R −1.00 0 0 15 ASB4_E89_F 0.85 0 0 16 ASB4_P391_F 0.96 0 0 17 BCAM_E100_R −0.57 0 0 18 BCAM_P205_F −1.18 0 0 19 BCL2L2_E172_F −0.64 0 0 20 BCL3_E71_F −0.91 0 0 21 BCL3_P1038_R −0.29 0 0 22 BMP2_E48_R −0.65 0 0 23 BMP3_P56_R −0.49 0 0 24 BMP4_P123_R −1.20 0 0 25 CARD15_P302_R −1.02 0 0 26 CD34_E20_R −0.61 0 0 27 CD9_E14_R −0.76 0 0 28 CDH1_P52_R −0.73 0 0 29 CDH11_P203_R −1.08 0 0 30 CDH11_P354_R −0.74 0 0 31 CDH13_E102_F −1.34 0 0 32 CDH13_P88_F −1.49 0 0 33 CDH17_E31_F 1.00 0 0 34 CDH3_P87_R 0.77 0 0 35 CDK10_E74_F −0.89 0 0 36 CEACAM1_P44_R 1.81 0 0 37 CHD2_P451_F 0.63 0 0 38 CHD2_P667_F 0.61 0 0 39 CLDN4_P1120_R 1.74 0 0 40 COL18A1_P494_R −1.50 0 0 41 COL1A1_P117_R −1.16 0 0 42 COL1A1_P5_F −1.44 0 0 43 COL6A1_P283_F −0.43 0 0 44 COPG2_P298_F 0.96 0 0 45 CPA4_P961_R 1.04 0 0 46 CRIP1_P874_R −1.02 0 0 47 CSF2_E248_R 0.92 0 0 48 CSF2_P605_F 1.23 0 0 49 CSF3_E242_R 0.71 0 0 50 CSF3_P309_R 1.48 0 0 51 CTNNA1_P382_R −0.69 0 0 52 CTSH_E157_R 0.77 0 0 53 CYP1B1_P212_F −0.87 0 0 54 DAB2_P35_F −1.10 0 0 55 DAPK1_E46_R −0.57 0 0 56 DAPK1_P10_F −0.86 0 0 57 DAPK1_P345_R −0.97 0 0 58 DBC1_E204_F −1.15 0 0 59 DDIT3_P1313_R 1.91 0 0 60 DDR2_E331_F −1.60 0 0 61 DDR2_P743_R −1.31 0 0 62 DIO3_P90_F −1.11 0 0 63 DLC1_P88_R 1.02 0 0 64 DLK1_E227_R −1.31 0 0 65 EFNA1_P7_F −0.44 0 0 66 EGFR_E295_R −0.63 0 0 67 ENC1_P484_R −0.58 0 0 68 EPHA5_E158_R −1.46 0 0 69 EPHA5_P66_F −0.91 0 0 70 EPHA7_E6_F −1.08 0 0 71 EPHA7_P205_R −0.98 0 0 72 EPHB1_E202_R −0.71 0 0 73 EPHB3_E0_F −0.98 0 0 74 EPHB4_E476_R −1.37 0 0 75 EPHB6_E342_F −1.36 0 0 76 EPO_P162_R −1.11 0 0 77 EPS8_E231_F −0.80 0 0 78 EPS8_P437_F −0.72 0 0 79 ERBB4_P541_F −0.91 0 0 80 ERCC1_P354_F −0.55 0 0 81 ERCC6_P698_R −1.11 0 0 82 FANCG_E207_R −0.70 0 0 83 FAT_P279_R −0.79 0 0 84 FER_E119_F −1.26 0 0 85 FES_E34_R −1.40 0 0 86 FES_P223_R −1.17 0 0 87 FGF12_E61_R −0.89 0 0 88 FGF2_P229_F −1.74 0 0 89 FGF5_E16_F −1.02 0 0 90 FGFR1_P204_F −1.16 0 0 91 FGFR2_P266_R −0.69 0 0 92 FGFR4_P610_F 0.66 0 0 93 FHIT_E19_R −0.57 0 0 94 FLI1_E29_F −1.27 0 0 95 FLJ20712_P984_R 1.27 0 0 96 FOLR1_E368_R 1.07 0 0 97 FRZB_E186_R −1.60 0 0 98 GALR1_E52_F −1.52 0 0 99 GALR1_P80_F −1.33 0 0 100 GAS7_E148_F −1.89 0 0 101 GFAP_P1214_F 0.59 0 0 102 GNG7_E310_R 0.54 0 0 103 GNG7_P903_F 0.58 0 0 104 GNMT_E126_F −0.90 0 0 105 GRB10_E85_R −0.68 0 0 106 GSTP1_seq_38_S153_R −0.67 0 0 107 H19_P1411_R 0.98 0 0 108 HDAC1_P414_R 1.38 0 0 109 HGF_E102_R −1.37 0 0 110 HIC1_P565_R −0.99 0 0 111 HIC-1_seq_48_S103_R 1.49 0 0 112 HLA-DOA_P191_R −1.06 0 0 113 HLA-DPA1_P28_R 1.48 0 0 114 HOXB13_P17_R −1.48 0 0 115 HSPA2_P162_R 0.80 0 0 116 HTR1B_P107_F −1.64 0 0 117 HTR1B_P222_F −2.03 0 0 118 HTR2A_P853_F −1.98 0 0 119 IFNGR1_P307_F 0.66 0 0 120 IGF1_P933_F 0.84 0 0 121 IGF1R_P325_R −0.46 0 0 122 IGF2R_P396_R −1.09 0 0 123 IGFBP5_E144_F −0.80 0 0 124 IGSF4C_E65_F −1.36 0 0 125 IL18BP_E285_F 0.88 0 0 126 IL1B_P829_F 0.89 0 0 127 INHA_P1144_R −0.92 0 0 128 INHA_P1189_F −0.77 0 0 129 ISL1_E87_R −1.29 0 0 130 ISL1_P554_F −1.40 0 0 131 ITGA2_E120_F −0.84 0 0 132 ITGA2_P26_R −0.71 0 0 133 ITGA6_P298_R −1.41 0 0 134 JAG2_E54_F −0.52 0 0 135 KRT1_P798_R 0.68 0 0 136 KRT13_P341_R 0.85 0 0 137 LAMB1_E144_R −0.93 0 0 138 LIG4_P194_F −0.59 0 0 139 LMTK2_P1034_F 0.56 0 0 140 LRP2_E20_F −0.47 0 0 141 MAF_P826_R −1.05 0 0 142 MAS1_P469_R 0.88 0 0 143 MCAM_P169_R −0.71 0 0 144 MCC_P196_R 0.48 0 0 145 MCM2_P260_F −0.97 0 0 146 MLH3_E72_F 0.70 0 0 147 MMP14_P208_R −1.05 0 0 148 MMP2_E21_R −1.30 0 0 149 MT1A_P600_F 1.24 0 0 150 MUSK_P308_F 0.94 0 0 151 NCL_P1102_F 1.05 0 0 152 NGFB_E353_F −1.40 0 0 153 NID1_P677_F 1.31 0 0 154 NID1_P714_R 1.02 0 0 155 NOS3_P38_F 0.97 0 0 156 NOTCH2_P312_R −0.41 0 0 157 NOTCH3_P198_R −1.05 0 0 158 NPR2_P618_F −1.19 0 0 159 NTRK3_E131_F −1.93 0 0 160 NTRK3_P636_R −1.70 0 0 161 NTRK3_P752_F −1.56 0 0 162 p16_seq_47_S85_F −0.79 0 0 163 PCDH1_E22_F −0.63 0 0 164 PDGFA_P841_R −0.54 0 0 165 PDGFRB_E195_R −1.38 0 0 166 PDGFRB_P273_F −1.10 0 0 167 PGR_P790_F 0.95 0 0 168 PI3_P1394_R 0.85 0 0 169 PLA2G2A_P528_F 0.98 0 0 170 PLAGL1_P334_F 1.09 0 0 171 PLAT_P80_F −1.54 0 0 172 PLG_E406_F 0.80 0 0 173 PLXDC2_P914_R −1.02 0 0 174 PMP22_P975_F 1.17 0 0 175 PRKCDBP_E206_F −1.11 0 0 176 PRKCDBP_P352_R −1.47 0 0 177 PRSS8_E134_R 0.95 0 0 178 PSCA_P135_F 1.17 0 0 179 PTCH_E42_F −0.68 0 0 180 PTCH2_P568_R −1.21 0 0 181 PTEN_P438_F −0.51 0 0 182 PTHLH_E251_F 0.83 0 0 183 PTHLH_P15_R 0.84 0 0 184 PTK6_E50_F 1.09 0 0 185 PTPRG_P476_F −0.46 0 0 186 RARB_E114_F −1.70 0 0 187 RARB_P60_F −1.31 0 0 188 RARRES1_P57_R −1.30 0 0 189 ROR2_E112_F −0.93 0 0 190 RUNX1T1_P103_F −1.22 0 0 191 S100A12_P1221_R 0.67 0 0 192 SEMA3C_P642_F 1.18 0 0 193 SEPT9_P374_F 1.43 0 0 194 SEPT9_P58_R 1.20 0 0 195 SERPINA5_E69_F 0.59 0 0 196 SFTPA1_E340_R 1.16 0 0 197 SFTPA1_P421_F 1.01 0 0 198 SFTPB_P689_R 1.32 0 0 199 SFTPC_E13_F 1.00 0 0 200 SFTPD_E169_F 0.78 0 0 201 SHH_P104_R −1.07 0 0 202 SLC22A18_P216_R 0.87 0 0 203 SLC22A2_P109_F 0.67 0 0 204 SLC22A3_P634_F 0.95 0 0 205 SLIT2_E111_R −1.41 0 0 206 SLIT2_P208_F −1.35 0 0 207 SMAD2_P708_R −0.37 0 0 208 SMAD4_P474_R −0.61 0 0 209 SMO_E57_F −1.41 0 0 210 SMO_P455_R −1.60 0 0 211 SPARC_E50_R −1.22 0 0 212 SPARC_P195_F −1.90 0 0 213 SPDEF_E116_R 1.22 0 0 214 SPI1_E205_F 0.49 0 0 215 SRC_E100_R 2.00 0 0 216 SRC_P164_F 1.17 0 0 217 SRC_P297_F 0.83 0 0 218 STAT5A_E42_F −1.36 0 0 219 STK11_P295_R −0.88 0 0 220 TGFA_P558_F −0.76 0 0 221 TGFB2_P632_F −0.59 0 0 222 TGFBI_P173_F −0.91 0 0 223 TGFBR3_E188_R −0.62 0 0 224 THPO_E483_F 0.94 0 0 225 THPO_P585_R 0.82 0 0 226 THY1_P20_R −1.07 0 0 227 TIAM1_P117_F −1.21 0 0 228 TIMP2_E394_R −0.46 0 0 229 TIMP2_P267_F −1.46 0 0 230 TIMP3_seq_7_S38_(—) −1.24 0 0 231 TJP2_P330_R −2.76 0 0 232 TJP2_P518_F −2.46 0 0 233 TMEFF1_E180_R −0.46 0 0 234 TMPRSS4_E83_F 2.02 0 0 235 TMPRSS4_P552_F 1.09 0 0 236 TNF_P1084_F 0.70 0 0 237 TNFRSF10C_E109_I 2.01 0 0 238 TNFRSF10C_P7_F 2.11 0 0 239 TNFSF10_E53_F 2.56 0 0 240 TNFSF10_P2_R 1.85 0 0 241 TPEF_seq_44_S36_(—) −1.13 0 0 242 TRPM5_P979_F 0.93 0 0 243 TSG101_P257_R −0.83 0 0 244 TUBB3_P364_F −0.63 0 0 245 TUBB3_P721_R −0.96 0 0 246 TWIST1_E117_R −2.42 0 0 247 UGT1A1_P564_R 0.66 0 0 248 USP29_E274_F 1.10 0 0 249 USP29_P205_R 0.63 0 0 250 WEE1_P924_R 1.32 0 0 251 WNT2B_P1185_R −0.90 0 0 252 WNT5A_E43_F −0.68 0 0 253 WNT8B_E487_F 0.93 0 0 254 WT1_E32_F −2.17 0 0 255 WT1_P853_F −2.42 0 0 256 XRCC2_P1077_F 1.51 0 0 257 YES1_P600_F −0.50 0 0 258 ASB4_P52_R 1.22 0 0 259 BMPR2_E435_F 0.61 0 0 260 CDH17_P376_F 0.85 0 0 261 DCC_P471_R −1.13 0 0 262 EDN1_E50_R 1.30 0 0 263 FLI1_P620_R −1.04 0 0 264 GLI2_P295_F 0.91 0 0 265 HGF_P1293_R 1.00 0 0 266 MFAP4_P197_F −1.00 0 0 267 NRG1_P558_R −0.79 0 0 268 TGFBI_P31_R −0.56 0 0 269 TPEF_seq_44_S88_(—) −1.44 0 0 270 TRAF4_P372_F −0.92 0 0 271 FGF5_P238_R −1.18 0 0 272 IFNG_E293_F 0.85 0 0 273 SLC22A3_P528_F 0.83 0 0 274 CASP6_P201_F −0.79 0 0 275 DHCR24_P406_R −0.87 0 0 276 CDH1_P45_F −0.79 0 0 277 GADD45A_P737_R −0.77 0 0 278 HLA-DPA1_E35_R 0.85 0 0 279 ISL1_P379_F −1.35 0 0 280 SERPINB2_P939_F 0.69 0 0 281 LAMC1_P808_F −0.48 0 0 282 TFDP1_P543_R 0.49 0 0 283 EIF2AK2_E103_R −0.68 0 0 284 PKD2_P287_R −0.55 0 0 285 ABCA1_E120_R −0.42 0 0 286 ACTG2_P455_R 0.57 0 0 287 NOS2A_E117_R 0.72 0 0 288 HPN_P823_F 0.64 0 0 289 IGF2_E134_R −1.11 0 0 290 SMARCA3_P109_R −0.90 0 0 291 ITGB1_P451_F −0.89 0 0 292 IGSF4_P454_F −0.65 0 0 293 PPARG_P693_F 0.60 0 0 294 DAB2IP_E18_R −0.95 0 0 295 CASP6_P230_R −0.67 0 0 296 LOX_P313_R −0.81 0 0 297 PRSS1_E45_R 0.72 0 0 298 ROR2_P317_R −0.79 0 0 299 LAMC1_E466_R −0.59 0 0 300 CD81_P211_F 1.26 0 0 301 SLC22A18_P472_R 0.60 0 0 302 ITGA6_P718_R 0.78 0 0 303 PCGF4_P760_R −0.99 0 0 304 VAV1_E9_F 1.08 0 0 305 GJB2_P791_R −0.96 0 0 306 MLH3_P25_F −1.09 0 0 307 PHLDA2_E159_R −0.55 0 0 308 PLXDC2_E337_F −1.12 0 0 309 EGFR_P260_R −0.67 0 0 310 AIM2_E208_F 0.64 0 0 311 FLT4_E206_F −0.74 0 0 312 PGR_E183_R 0.72 0 0 313 GPX1_E46_R −0.70 0 0 314 JAG1_P66_F −0.68 0 0 315 NEFL_E23_R −1.18 0 0 316 PDGFRA_P1429_F −1.31 0 0 317 RAB32_E314_R −0.72 0 0 318 MAF_E77_R −0.77 0 0 319 NGFB_P13_F −0.74 0 0 320 PTGS1_P2_F −0.71 0 0 321 SKI_E465_R −0.54 0 0 322 GRB10_P496_R 0.91 0 0 323 TNC_P57_F −0.67 0 0 324 PTHLH_P757_F 0.53 0 0 325 TDGF1_E53_R 0.58 0 0 326 PLAU_P11_F −0.75 0 0 327 MGMT_P272_R −1.00 0 0 328 SEMA3F_E333_R −0.61 0 0 329 CTNNA1_P185_R −0.70 0 0 330 TNFRSF10B_E198_I −0.70 0 0 331 P2RX7_E323_R −0.98 0 0 332 TJP1_P326_R −0.54 0 0 333 CSF1_P217_F 0.49 0 0 334 COL6A1_P425_F −0.82 0 0 335 HOXB13_E21_F −1.12 0 0 336 BMP4_P199_R −0.83 0 0 337 SEMA3B_E96_F −0.55 0 0 338 RASA1_E107_F −0.64 0 0 339 FGFR2_P460_R −0.83 0 0 340 P2RX7_P119_R −0.88 0 0 341 PALM2-AKAP2_P42 −0.80 0 0 342 VEGFB_P658_F −0.59 0 0 343 PLG_P370_F 0.45 0 0 344 CAV1_P130_R −0.72 0 0 345 MFAP4_P10_R −0.74 0 0 346 TP73_P496_F −0.66 0 0 347 SNRPN_seq_18_S9 0.66 0 0 348 FGF9_P862_R −0.48 0 0 349 CTSH_P238_F −0.53 0 0 350 THBS2_P605_R 1.13 0 0 351 DMP1_E194_F 0.54 0 0 352 NTRK2_P10_F −1.48 0 0 353 INSR_E97_F −0.57 0 0 354 CCKAR_P270_F 0.60 0 0 355 CAV1_P169_F −0.60 0 0 356 CSPG2_E38_F −1.11 0 0 357 TGFA_P642_R −0.53 0 0 358 PLAGL1_P236_R 0.63 0 0 359 PCGF4_P92_R −0.88 0 0 360 TWIST1_P44_R −1.32 0 0 361 ID1_P880_F −0.61 0 0 362 TFPI2_P9_F −0.83 0 0 363 GDF10_E39_F −0.67 0 0 364 MALT1_P406_R −0.74 0 0 365 NKX3-1_P146_F −0.43 0 0 366 MAS1_P657_R 0.64 0 0 367 APBA2_P305_R 0.65 0 0 368 TUSC3_E29_R −0.95 0 0 369 CXCL9_E268_R 0.73 0 0 370 MME_P388_F −1.08 0 0 371 HDAC11_P556_F −0.28 0 0 372 OAT_P465_F −0.93 0 0 373 IL2_P607_R 0.59 0 0 374 WNT2_P217_F −0.86 0 0 375 DSG1_P159_R 0.61 0 0 376 MLF1_P97_F −1.35 0 0 377 ITGB4_E144_F −0.57 0 0 378 HOXA5_E187_F −1.15 0 0 379 GABRB3_E42_F −1.16 0 0 380 DMP1_P134_F 0.59 0 0 381 MAP2K6_E297_F −0.90 0 0 382 PTPNS1_P301_R −0.52 0 0 383 ABCC5_P444_F −0.39 0 0 384 PSIP1_P163_R −0.85 0 0 385 TYRO3_P366_F −0.56 0 0 386 NRAS_P103_R −0.49 0 0 387 RUNX1T1_E145_R −0.92 0 0 388 SPP1_P647_F 0.76 0 0 389 KLK11_P103_R 0.64 0 0 390 WNT5A_P655_F −0.51 0 0 391 KDR_E79_F −0.66 0 0 392 SLC14A1_E295_F 0.69 0 0 393 PTK7_E317_F −0.81 0 0 394 EPHA3_E156_R −0.78 0 0 395 TEK_P479_R −0.73 0 0 396 BLK_P14_F 0.60 0 0 397 RARRES1_E235_F −1.18 0 0 398 EFNB3_P442_R −0.55 0 0 399 TGFB1_P833_R 0.64 0 0 400 MEST_P62_R 1.26 0 0 401 TNFRSF10D_P70_F 1.78 0 0 402 NAT2_P11_F 0.59 0 0 403 SPI1_P48_F 0.83 0 0 404 CSPG2_P82_R −0.91 0 0 405 KLF5_P13_F −0.57 0 0 406 PDE1B_E141_F −0.40 0 0 407 GLI3_P453_R −0.67 0 0 408 VAMP8_E7_F −0.62 0 0 409 DSP_P36_F −1.04 0 0 410 TYK2_P494_F −0.58 0 0 411 FLT3_P302_F −1.15 0 0 412 SFRP1_E398_R −1.05 0 0 413 DAB2IP_P9_F −0.76 0 0 414 GML_P281_R 0.99 0 0 415 LMO2_P794_R −1.18 0 0 416 CTGF_E156_F −0.51 0 0 417 KDR_P445_R −1.05 0 0 418 AHR_E103_F −0.29 0 0 419 ABCG2_P178_R −0.56 0 0 420 CD81_P272_R 0.77 0 0 421 HPSE_P29_F −0.85 0 0 422 PDGFB_E25_R −0.48 0 0 423 CCR5_P630_R −0.54 0 0 424 PKD2_P336_R −0.50 0 0 425 CCND3_P435_F −0.50 0 0 426 HDAC5_E298_F −0.46 0 0 427 NDN_P1110_F 0.65 0 0 428 GATA6_P21_R −0.87 0 0 429 IL1B_P582_R −1.01 0 0 430 TRIP6_P1090_F −0.88 0 0 431 BSG_P211_R 2.78 0 0 432 JUNB_P1149_R −0.38 0 0 433 IGFBP6_P328_R −0.63 0 0 434 GAS1_P754_R −1.08 0 0 435 EFNB3_E17_R −0.36 0 0 436 IL18BP_P51_R 0.68 0 0 437 MAP3K1_P7_F 1.53 0 0 438 CD1A_P414_R 0.64 0 0 439 PDGFRB_P343_F −0.99 0 0 440 CD34_P339_R 0.55 0 0 441 CDKN1C_P6_R −0.67 0 0 442 SMARCA3_P17_R −0.69 0 0 443 BCR_P422_F 0.65 0 0 444 NTSR1_P318_F −1.13 0 0 445 SEMA3F_P692_R −0.51 0 0 446 MYCN_E77_R −0.79 0 0 447 GFAP_P56_R 0.67 0 0 448 MCM6_E136_F −0.56 0 0 449 PTPRH_E173_F 0.72 0 0 450 GAS1_E22_F −1.01 0 0 451 ABCC2_P88_F 0.65 0 0 452 TJP1_P390_F −0.59 0 0 453 CDH11_E102_R −0.43 0 0 454 BCL2A1_P1127_R 0.69 0 0 455 CD9_P504_F 1.17 0 0 456 ICAM1_P119_R −0.87 0 0 457 CEACAM1_E57_R 1.48 0 0 458 VAMP8_P241_F 0.72 0 0 459 YES1_P216_F −0.73 0 0 460 GPR116_P850_F 0.47 0 0 461 THBS1_P500_F −0.60 0 0 462 HHIP_E94_F −0.64 0 0 463 SEMA3B_P110_R −0.48 0 0 464 ADCYAP1_E163_R −0.79 0 0 465 CTLA4_E176_R 0.55 0 0 466 PTPNS1_E433_R −0.71 0 0 467 PRDM2_P1340_R 0.47 0 0 468 p16_seq_47_S188_R −1.41 0 0 469 HBII-13_P991_R 0.65 0 0 470 MLH1_P381_F −0.91 0 0 471 HBII-52_P659_F 0.71 0 0 472 KLF5_E190_R −0.70 0 0 473 PODXL_P1341_R −1.12 0 0 474 SEMA3C_E49_R −0.63 0 0 475 SHB_P473_R −0.62 0 0 476 SNCG_P98_R −0.60 0 0 477 LOX_P71_F −0.59 0 0 478 HLA-DPB1_P540_F 0.55 0 0 479 AOC3_P890_R 0.60 0 0 480 IRF5_E101_F −0.57 0 0 481 MCM2_P241_R −0.46 0 0 482 TRIM29_P261_F −1.07 0 0 483 HS3ST2_P546_F −0.75 0 0 484 PDGFB_P719_F 0.54 0 0 485 FVT1_P225_F −0.60 0 0 486 JAK3_P1075_R 0.61 0 0 487 MTA1_P478_F −0.68 0 0 488 TRPM5_E87_F 0.59 0 0 489 MAP3K9_E17_R −0.90 0 0 490 FANCA_P1006_R 0.61 0 0 491 AREG_E25_F −0.33 0 0 492 EDNRB_P709_R 0.84 0 0 493 WNT10B_P993_F 1.00 0 0 494 ZMYND10_P329_F −0.71 0 0 495 ARHGAP9_P260_F 0.69 0 0 496 NRG1_E74_F −0.50 0 0 497 KLK11_P1290_F 0.49 0 0 498 IGF2AS_E4_F −0.62 0 0 499 PTPRH_P255_F 0.86 0 0 500 SEMA3A_P343_F −0.74 0 0 501 PIK3R1_P307_F 0.38 0 0 502 EYA4_E277_F −1.04 0 0 503 SERPINA5_P156_F 0.61 0 0 504 HPN_P374_R 0.51 0 0 505 ABL1_P53_F −0.50 0 0 506 CTSL_P81_F −0.60 0 0 507 VIM_P343_R −0.58 0 0 508 SFRP1_P157_F −1.34 0 0 509 CCND1_E280_R −0.57 0 0 510 ZIM2_P22_F −0.64 0 0 511 CHI3L2_E10_F −0.58 0 0 512 HBII-52_E142_F 0.70 0 0 513 GATA6_P726_F −0.78 0 0 514 IRF5_P123_F −0.30 0 0 515 PPP2R1B_P268_R −0.37 0 0 516 ALPL_P433_F 0.68 0 0 517 CDK10_P199_R 0.61 0 0 518 MMP8_E89_R 0.57 0 0 519 GLI3_E148_R 0.58 0 0 520 TNFRSF10D_E27_F 2.02 0 0 521 SERPINE1_P519_F −0.63 0 0 522 ACTG2_P346_F 0.57 0 0 523 DAB2_P468_F −0.87 0 0 524 GRB10_P260_F −0.62 0 0 525 VAV2_P1182_F 0.26 0 0 526 SMARCA4_P362_R −0.31 0 0 527 MGMT_P281_F −1.04 0 0 528 EPHB2_E297_F −0.57 0 0 529 PARP1_P610_R 0.63 0 0 530 NEO1_P1067_F −0.60 0 0 531 JAG2_P264_F −0.37 0 0 532 FGF12_P210_R −0.96 0 0 533 GABRB3_P92_F −0.57 0 0 534 IRF7_E236_R −0.61 0 0 535 PYCARD_P393_F −0.59 0 0 536 P2RX7_P597_F 0.79 0 0 537 CDKN1A_E101_F −0.45 0 0 538 NTSR1_E109_F −0.92 0 0 539 MEST_P4_F 1.10 0 0 540 PAX6_P1121_F 1.05 0 0 541 PTPRO_E56_F −1.16 0 0 542 VAV1_P317_F 0.65 0 0 543 RHOH_P953_R 0.37 0 0 544 PTPRF_E178_R −0.44 0 0 545 WNT2B_P1195_F −0.46 0 0 546 BMP3_E147_F −0.66 0 0 547 SOX1_P1018_R −1.05 0 0 548 DST_P262_R −0.47 0 0 549 HLA-DPA1_P205_R 0.82 0 0 550 CRIP1_P274_F −0.39 0 0 551 LCK_E28_F 0.47 0 0 552 FANCF_P13_F −0.42 0 0 553 MLLT3_E93_R −0.25 0 0 554 DCC_P177_F −0.94 0 0 555 S100A4_P887_R 0.42 0 0 556 MEST_E150_F 1.01 0 0 557 PLXDC1_E71_F −0.44 0 0 558 ONECUT2_E96_F −0.70 0 0 559 CYP2E1_P416_F 0.84 0 0 560 MLF1_E243_F −0.67 0 0 561 ADCYAP1_P398_F −0.95 0 0 562 ABCC2_E16_R 1.13 0 0 563 PROK2_E0_F −0.58 0 0 564 ABCA1_P45_F −0.49 0 0 565 MCC_E23_R −0.41 0 0 566 ACVR1C_P115_R −0.71 0 0 567 KCNQ1_P546_R 0.66 0 0 568 HBII-52_P563_F 0.63 0 0 569 TMEFF2_P210_R −0.79 0 0 570 UGT1A1_P315_R 0.48 0 0 571 KRT13_P676_F 0.34 0 0 572 GPX1_P194_F −0.81 0 0 573 APBA1_P644_F −0.33 0 0 574 GML_E144_F 1.05 0 0 575 TNK1_P221_F −0.57 0 0 576 APOC1_P406_R 0.40 0 0 577 CCKBR_P361_R −0.64 0 0 578 TYRO3_P501_F −0.43 0 0 579 RET_seq_54_S260_F −1.08 0 0 580 TESK2_P252_R −0.32 0 0 581 SLC22A3_E122_R −0.85 0 0 582 MXI1_P75_R −0.76 0 0 583 EPHB2_P165_R −0.72 0 0 584 CDH17_P532_F 0.39 0 0 585 EFNA1_P591_R −0.29 0 0 586 TUSC3_P85_R −0.70 0 0 587 TCF4_P175_R −0.90 0 0 588 ERG_E28_F −0.90 0 0 589 ETS2_P835_F 1.44 0 0 590 FRZB_P406_F −1.17 0 0 591 FYN_P352_R −0.55 0 0 592 SPI1_P929_F 0.44 0 0 593 NFKB2_P709_R −0.41 0 0 594 FOSL2_E384_R −0.56 0 0 595 CSF1_P339_F −0.34 0 0 596 COL18A1_P365_R −0.59 0 0 597 ELL_P693_F 0.64 0 0 598 GAS7_P622_R −0.76 0 0 599 HLA-DPB1_E2_R 0.72 0 0 600 MMP14_P13_F −0.70 0 0 601 FGF6_P139_R 0.57 0 0 602 DNMT1_P100_R 0.43 0 0 603 MOS_E60_R −1.02 0 0 604 ZNFN1A1_E102_F 0.55 0 0 605 RBP1_E158_F −0.89 0 0 606 NOS2A_P288_R 0.51 0 0 607 DIO3_P674_F −0.83 0 0 608 GNAS_P86_F 0.39 0 0 609 SLC5A8_P38_R 1.06 0 0 610 MKRN3_P108_F 0.61 0 0 611 TM7SF3_P1068_R 0.61 0 0 612 DLL1_P832_F −0.68 0 0 613 HPSE_P93_F −0.83 0 0 614 CHFR_P501_F −0.74 0 0 615 RARA_P1076_R −0.62 0 0 616 GJB2_E43_F −0.68 0 0 617 SEZ6L_P299_F −1.03 0 0 618 MSH2_P1008_F 0.49 0 0 619 ETV6_E430_F 0.41 0 0 620 ITPR3_P1112_F 0.22 0 0 621 NDN_E131_R 0.39 0 0 622 APOC2_P377_F 0.39 0 0 623 FLT1_E444_F −0.69 0 0 624 DUSP4_P925_R −0.55 0 0 625 GUCY2D_P48_R −0.66 0 0 626 EDNRB_P148_R 0.57 0 0 627 KIAA1804_P689_R 1.23 0 0 628 AATK_E63_R 0.63 0 0 629 ETS1_E253_R −0.37 0 0 630 MPO_P883_R −0.71 0 0 631 TGFB2_E226_R −0.50 0 0 632 INS_P248_F 0.49 0 0 633 MME_E29_F −0.57 0 0 634 SMARCB1_P220_R −0.44 0 0 635 CTSL_P264_R −0.55 0 0 636 FHIT_P93_R −0.45 0 0 637 CD1A_P6_F 0.63 0 0 638 RAB32_P493_R 0.71 0 0 639 CRK_P721_F 0.57 0 0 640 JAK2_P772_R −0.67 0 0 641 SFN_E118_F 0.63 0 0 642 IL12B_P392_R 0.65 0 0 643 PLAUR_P82_F −0.29 0 0 644 ERBB4_P255_F −0.43 0 0 645 MMP9_P237_R −0.59 0 0 646 IL16_P93_R −0.55 0 0 647 WRN_P969_F 0.57 0 0 648 IFNGR2_P377_R −0.65 0 0 649 FGF8_P473_F −0.75 0 0 650 PGR_P456_R 0.53 0 0 651 TMEM63A_E63_F 0.28 0 0 652 PALM2-AKAP2_P183_R −0.39 0 0 653 IFNGR2_E164_F −0.35 0 0 654 PI3_E107_F 0.84 0 0 655 NTRK2_P395_R −1.05 0 0 656 FAS_P322_R −0.40 0 0 657 XRCC1_P681_R 0.48 0 0 658 PITX2_E24_R −0.74 1.00E−06 0 659 IGFBP3_E65_R 0.53 1.00E−06 0 660 MYCN_P464_R −0.21 1.00E−06 0 661 MAPK9_P1175_F 0.46 1.00E−06 0 662 TCF7L2_P193_R −0.46 1.00E−06 0 663 DDR1_E23_R −0.40 1.00E−06 0 664 FANCE_P356_R 1.10 1.00E−06 0 665 SOD3_P460_R −0.50 1.00E−06 0 666 SYK_P584_F 0.55 1.00E−06 0 667 GNMT_P197_F −0.39 1.00E−06 0 668 NQO1_E74_R −0.23 1.00E−06 0 669 MYOD1_P50_F −0.67 1.00E−06 0 670 FGF1_E5_F 0.52 1.00E−06 0 671 ERN1_P809_R 0.70 1.00E−06 0 672 MPL_P657_F 0.39 1.00E−06 0 673 NEU1_P745_F −0.60 1.00E−06 0 674 MDR1_seq_42_S300_R −1.23 1.00E−06 0 675 UGT1A1_E11_F 0.46 1.00E−06 0 676 NQO1_P345_R −0.40 1.00E−06 0 677 SEZ6L_P249_F −1.00 1.00E−06 0 678 FGF3_P171_R −1.01 1.00E−06 0 679 TP73_E155_F −0.49 1.00E−06 0 680 FLT1_P302_F −0.85 1.00E−06 0 681 TDG_E129_F 0.37 1.00E−06 0 682 ADCYAP1_P455_R −0.80 1.00E−06 0 683 PTCH2_P37_F −0.43 1.00E−06 0 684 IGSF4_P86_R −0.71 1.00E−06 0 685 MMP1_P397_R 0.57 1.00E−06 0 686 CD9_P585_R 0.67 1.00E−06 0 687 MAP3K1_E81_F 1.12 1.00E−06 0 688 DSC2_P407_R 0.40 1.00E−06 0 689 ETV1_P515_F −0.66 1.00E−06 0 690 TEK_E75_F −0.67 1.00E−06 0 691 PRSS1_P1249_R 0.49 1.00E−06 0 692 TMEFF2_P152_R −0.72 1.00E−06 0 693 EPM2A_P64_R −0.16 1.00E−06 0 694 IL13_E75_R 0.37 1.00E−06 0 695 BRCA1_P835_R 0.58 1.00E−06 0 696 ABCG2_P310_R 1.38 1.00E−06 0 697 TMEFF1_P234_F −0.53 1.00E−06 0 698 ZIM3_P451_R 0.54 2.00E−06 0 699 IHH_P246_R −0.52 2.00E−06 0 700 F2R_P88_F −0.55 2.00E−06 0 701 IGF2_P1036_R −0.61 2.00E−06 0 702 GDF10_P95_R −0.68 2.00E−06 0 703 BMPR2_P1271_F −0.34 2.00E−06 0 704 TNFRSF1B_E5_F −0.31 2.00E−06 0 705 EVI1_E47_R 1.19 2.00E−06 0 706 SLC22A2_E271_R 0.44 2.00E−06 1.00E−06 707 INS_P804_R 0.54 2.00E−06 1.00E−06 708 DIO3_E230_R −0.57 2.00E−06 1.00E−06 709 CDKN1B_P1161_F 1.10 2.00E−06 1.00E−06 710 DDR1_P332_R 0.60 2.00E−06 1.00E−06 711 TWIST1_P355_R −0.68 3.00E−06 1.00E−06 712 AFF3_P122_F 0.64 3.00E−06 1.00E−06 713 ITGB4_P517_F −0.38 3.00E−06 1.00E−06 714 ST6GAL1_P164_R −0.66 3.00E−06 1.00E−06 715 TNK1_P41_R −0.51 3.00E−06 1.00E−06 716 ODC1_P424_F −0.31 3.00E−06 1.00E−06 717 ROR1_P6_F −0.32 3.00E−06 1.00E−06 718 MAPK12_E165_R −0.40 3.00E−06 1.00E−06 719 CTNNB1_P757_F 0.72 4.00E−06 1.00E−06 720 IL17RB_P788_R −0.38 4.00E−06 1.00E−06 721 PEG10_P978_R −0.59 4.00E−06 1.00E−06 722 RET_seq_53_S374_(—) −0.99 4.00E−06 1.00E−06 723 DES_E228_R 0.64 4.00E−06 1.00E−06 724 THBS1_E207_R 1.19 4.00E−06 1.00E−06 725 IL6_E168_F −0.53 4.00E−06 1.00E−06 726 CD34_P780_R 0.37 5.00E−06 1.00E−06 727 SNRPN_P230_R 0.36 5.00E−06 1.00E−06 728 DCN_P1320_R 0.62 5.00E−06 1.00E−06 729 IGFBP7_P297_F −0.63 5.00E−06 1.00E−06 730 FABP3_P598_F −0.52 5.00E−06 1.00E−06 731 DNAJC15_E26_R 0.52 6.00E−06 1.00E−06 732 CSF3R_P472_F 0.39 6.00E−06 1.00E−06 733 CYP2E1_E53_R 0.50 6.00E−06 1.00E−06 734 CCNE1_P683_F −0.19 6.00E−06 1.00E−06 735 GPR116_E328_R 0.56 6.00E−06 1.00E−06 736 CCNA1_P216_F −0.86 6.00E−06 1.00E−06 737 NPY_E31_R −0.61 6.00E−06 1.00E−06 738 CPNE1_P138_F −0.81 6.00E−06 1.00E−06 739 FGF7_P44_F −0.57 6.00E−06 1.00E−06 740 GSTM2_E153_F 0.97 7.00E−06 1.00E−06 741 FGR_P39_F 0.49 7.00E−06 2.00E−06 742 FN1_P229_R 0.43 7.00E−06 2.00E−06 743 EXT1_E197_F −0.39 7.00E−06 2.00E−06 744 CTTN_E29_R −0.44 7.00E−06 2.00E−06 745 TBX1_P520_F −0.45 7.00E−06 2.00E−06 746 CSK_P740_R −0.47 8.00E−06 2.00E−06 747 POMC_P400_R 0.66 8.00E−06 2.00E−06 748 PLAT_E158_F −0.55 8.00E−06 2.00E−06 749 OGG1_E400_F −0.52 9.00E−06 2.00E−06 750 HRASLS_P353_R 0.41 1.00E−05 2.00E−06 751 ACVR1B_E497_R −0.54 1.00E−05 2.00E−06 752 TES_P182_F 0.77 1.10E−05 2.00E−06 753 NOTCH1_P1198_F −0.40 1.10E−05 2.00E−06 754 CAPG_E228_F −0.48 1.10E−05 2.00E−06 755 MAP3K8_P1036_F 0.48 1.10E−05 2.00E−06 756 TIAM1_P188_R −0.55 1.10E−05 3.00E−06 757 HLA-DQA2_P282_R 0.41 1.30E−05 3.00E−06 758 COL4A3_P545_F −0.38 1.30E−05 3.00E−06 759 CCND2_P887_F −1.07 1.30E−05 3.00E−06 760 AXL_P223_R 0.54 1.50E−05 3.00E−06 761 MDS1_E45_F 0.39 1.50E−05 3.00E−06 762 MMP9_E88_R 0.43 1.50E−05 3.00E−06 763 HIC1_E151_F −0.30 1.50E−05 3.00E−06 764 CARD15_P665_F 0.44 1.50E−05 3.00E−06 765 PTHR1_E36_R 0.32 1.60E−05 3.00E−06 766 EGF_P413_F 0.47 1.60E−05 4.00E−06 767 PPAT_E170_R 0.32 1.60E−05 4.00E−06 768 ACVR1B_P572_R −0.52 1.70E−05 4.00E−06 769 CD86_P3_F −0.68 1.80E−05 4.00E−06 770 LIF_P383_R −0.37 1.90E−05 4.00E−06 771 HBEGF_P32_R −0.54 2.00E−05 4.00E−06 772 MUC1_E18_R 0.42 2.00E−05 4.00E−06 773 MAGEL2_P170_R 0.43 2.00E−05 4.00E−06 774 HHIP_P307_R −0.59 2.10E−05 5.00E−06 775 TNF_P158_F 0.56 2.20E−05 5.00E−06 776 CFTR_P372_R −0.57 2.20E−05 5.00E−06 777 LTA_P214_R 0.38 2.30E−05 5.00E−06 778 CCL3_P543_R −0.50 2.30E−05 5.00E−06 779 NEFL_P209_R −0.59 2.30E−05 5.00E−06 780 EYA4_P794_F 0.53 2.30E−05 5.00E−06 781 TERT_P360_R −0.70 2.30E−05 5.00E−06 782 HOXA5_P1324_F 0.54 2.50E−05 6.00E−06 783 EIF2AK2_P313_F 1.22 2.50E−05 6.00E−06 784 TFF1_P180_R 0.41 2.70E−05 6.00E−06 785 AFF3_P808_F 0.53 2.80E−05 6.00E−06 786 NPR2_P1093_F −0.53 2.90E−05 6.00E−06 787 IGFBP6_E47_F 0.20 3.00E−05 6.00E−06 788 TMEFF2_E94_R −0.49 3.00E−05 6.00E−06 789 UGT1A7_P751_R 0.28 3.20E−05 7.00E−06 790 CTLA4_P1128_F 0.31 3.20E−05 7.00E−06 791 TBX1_P885_R −0.77 3.20E−05 7.00E−06 792 DNAJC15_P65_F 0.40 3.60E−05 8.00E−06 793 FGF3_E198_R −0.93 3.70E−05 8.00E−06 794 PTGS2_P308_F −0.34 3.70E−05 8.00E−06 795 MMP1_P460_F 0.40 3.80E−05 8.00E−06 796 MOS_P27_R −0.57 3.90E−05 8.00E−06 797 GPX3_E178_F −0.33 4.20E−05 9.00E−06 798 EGR4_E70_F −0.37 4.30E−05 9.00E−06 799 RAD54B_P227_F −0.45 4.50E−05 9.00E−06 800 USP29_P282_R 0.24 4.50E−05 9.00E−06 801 IL8_P83_F −0.48 4.70E−05 1.00E−05 802 SYK_E372_F 0.95 4.90E−05 1.00E−05 803 CASP8_E474_F −0.41 5.30E−05 1.10E−05 804 NGFR_E328_F −0.62 5.30E−05 1.10E−05 805 HLA-F_E402_F −0.65 5.50E−05 1.20E−05 806 FGF9_P1404_F −0.18 6.10E−05 1.30E−05 807 CSTB_E410_F −0.60 6.20E−05 1.30E−05 808 FAT_P973_R −0.44 6.20E−05 1.30E−05 809 MYH11_P22_F −0.87 6.40E−05 1.30E−05 810 FN1_E469_F 0.85 6.40E−05 1.30E−05 811 ESR2_P162_F −0.54 6.60E−05 1.40E−05 812 CLX1_P538_F 0.40 6.70E−05 1.40E−05 813 BMPR1A_P956_F −0.25 6.90E−05 1.50E−05 814 FASTK_P257_F −0.42 7.00E−05 1.50E−05 815 IL1A_E113_R 0.27 7.90E−05 1.70E−05 816 PTCH2_E173_F −0.43 8.10E−05 1.70E−05 817 ETS2_P684_F 1.23 8.40E−05 1.70E−05 818 RARRES1_P426_R −0.42 8.40E−05 1.80E−05 819 EPHX1_P1358_R 0.35 8.50E−05 1.80E−05 820 IGF1_E394_F −0.46 8.60E−05 1.80E−05 821 LIG3_P622_R 0.43 9.20E−05 1.90E−05 822 TRIP6_P1274_R −0.48 9.40E−05 1.90E−05 823 FGFR1_E317_F −0.25 9.60E−05 2.00E−05 824 DST_E31_F −0.22 0.000102 2.10E−05 825 BDNF_P259_R −0.49 0.000105 2.20E−05 826 PWCR1_P811_F 0.40 0.000112 2.30E−05 827 SEMA3A_P658_R −0.34 0.000113 2.30E−05 828 CSF1R_E26_F 0.47 0.000114 2.30E−05 829 HS3ST2_P171_F −0.59 0.00012 2.50E−05 830 ERBB3_P870_R −0.33 0.000122 2.50E−05 831 TRPM5_P721_F 0.40 0.000123 2.50E−05 832 CASP10_P186_F −0.45 0.000128 2.60E−05 833 CDKN1A_P242_F −0.80 0.000131 2.70E−05 834 CASP3_P420_R −0.27 0.000132 2.70E−05 835 SNCG_P53_F −0.46 0.000147 3.00E−05 836 OPCML_P71_F −0.45 0.000149 3.00E−05 837 DSP_P440_R 0.67 0.000158 3.20E−05 838 PLXDC1_P236_F −0.49 0.00016 3.20E−05 839 ACVR2B_P676_F −0.32 0.000161 3.30E−05 840 SLC5A8_E60_R 0.54 0.00017 3.40E−05 841 DCC_E53_R −0.44 0.000178 3.60E−05 842 IL3_P556_F 0.21 0.000181 3.70E−05 843 TSG101_P139_R −0.22 0.000183 3.70E−05 844 MPL_P62_F 0.27 0.000187 3.80E−05 845 SERPINE1_E189_R −0.33 0.000189 3.80E−05 846 TCF4_P317_F −0.58 0.000197 4.00E−05 847 KRT5_E196_R −0.61 0.000205 4.10E−05 848 BCL2L2_P280_F −0.33 0.000206 4.10E−05 849 NNAT_P544_R 0.26 0.000207 4.10E−05 850 PTGS1_E80_F −0.57 0.000207 4.10E−05 851 PCDH1_P264_F −0.43 0.000233 4.60E−05 852 PDE1B_P263_R −0.62 0.000244 4.90E−05 853 EVI1_P30_R 0.93 0.000261 5.20E−05 854 SNCG_E119_F −0.37 0.000268 5.30E−05 855 CASP10_E139_F −0.36 0.000303 6.00E−05 856 ETS1_P559_R −0.23 0.000305 6.00E−05 857 CTSD_P726_F 0.33 0.000313 6.20E−05 858 HOXB2_P488_R −0.52 0.000313 6.20E−05 859 LEFTY2_P719_F 0.27 0.000324 6.40E−05 860 HDAC9_P137_R 0.59 0.000327 6.50E−05 861 WNT8B_P216_R 0.23 0.000366 7.20E−05 862 PDGFA_P78_F −0.18 0.000379 7.50E−05 863 DLL1_P386_F −0.46 0.000382 7.50E−05 864 CCND2_P898_R −0.78 0.000389 7.70E−05 865 NES_P239_R −0.36 0.00039 7.70E−05 866 SH3BP2_E18_F −0.32 0.000408 8.00E−05 867 MMP10_E136_R 0.39 0.000422 8.30E−05 868 OPCML_E219_R −0.64 0.000435 8.50E−05 869 CCKBR_P480_F −0.72 0.000436 8.50E−05 870 F2R_P839_F 0.31 0.000436 8.50E−05 871 LAT_E46_F 0.39 0.000452 8.80E−05 872 CDK2_P330_R −0.23 0.000453 8.80E−05 873 ZNFN1A1_P179_F 0.35 0.00046 8.90E−05 874 FLT3_E326_R −0.68 0.000485 9.40E−05 875 DSC2_E90_F −0.38 0.000487 9.50E−05 876 E2F5_P516_R −0.32 0.000507 9.80E−05 877 RRAS_P100_R −0.34 0.000521 0.000101 878 TSC2_E140_F 0.43 0.000531 0.000103 879 PPARG_E178_R −0.44 0.000565 0.000109 880 FABP3_E113_F −0.56 0.000577 0.000111 881 NKX3-1_P871_R 0.34 0.000583 0.000112 882 IGF2_P36_R −0.39 6.00E−04 0.000116 883 RARA_E128_R −0.36 0.000608 0.000117 884 CHFR_P635_R −0.22 0.000612 0.000118 885 EPHA3_P106_R −0.59 0.000617 0.000118 886 AHR_P166_R −0.52 0.000618 0.000118 887 TK1_E47_F 0.26 0.000626 0.00012 888 DHCR24_P652_R −0.25 0.000671 0.000128 889 RIPK1_P744_R 0.48 0.000676 0.000129 890 SOX17_P303_F −0.52 0.000693 0.000132 891 IGFBP5_P9_R −0.42 0.00071 0.000135 892 EPHA8_P256_F −0.34 0.000723 0.000138 893 CDK6_P291_R −0.33 0.000734 0.00014 894 TRIP6_E33_F −0.31 0.000748 0.000142 895 SERPINB5_P19_R 0.53 0.000754 0.000143 896 MYOD1_E156_F −0.49 0.000763 0.000145 897 PYCARD_E87_F −0.53 0.000778 0.000147 898 TIMP3_P690_R 0.19 0.000798 0.000151 899 UNG_P170_F −0.50 0.000824 0.000156 900 BCR_P346_F 0.38 0.000844 0.000159 901 AGXT_E115_R 0.38 0.00089 0.000168 902 KIT_P405_F −0.52 0.000922 0.000174 903 CHGA_P243_F −0.38 0.000939 0.000177 904 BMP6_P398_F −0.55 0.000966 0.000181 905 PLAGL1_E68_R −0.39 0.001001 0.000188 906 EPHB4_P313_R −0.24 0.001022 0.000191 907 MMP7_P613_F 0.16 0.001022 0.000191 908 RHOC_P536_F −0.41 0.001074 0.000201 909 RBP1_P150_F −0.62 0.001094 0.000204 910 CFTR_P115_F −0.65 0.001105 0.000206 911 SNURF_P2_R 0.23 0.001129 0.000211 912 TSP50_E21_R 0.31 0.001207 0.000225 913 RAF1_P330_F −0.50 0.001293 0.000241 914 PAX6_E129_F −0.65 0.001332 0.000247 915 LRRK1_P39_F −0.20 0.001332 0.000247 916 IPF1_P750_F −0.48 0.001343 0.000249 917 PEG3_E496_F 0.24 0.00138 0.000256 918 FLT4_P180_R −0.63 0.001382 0.000256 919 COL1A2_P407_R 0.40 0.001398 0.000258 920 PPARD_P846_F −0.36 0.001406 0.00026 921 DBC1_P351_R −0.52 0.001464 0.00027 922 ST6GAL1_P226_F −0.63 0.001498 0.000276 923 CHI3L2_P226_F −0.36 0.001605 0.000296 924 MEG3_P235_F −0.35 0.001649 0.000303 925 DLC1_E276_F 0.45 0.001745 0.000321 926 RARA_P176_R −0.36 0.001819 0.000334 927 CDKN2B_seq_50_S −0.34 0.001832 0.000336 928 ZMYND10_E77_R −0.31 0.001937 0.000355 929 PGF_P320_F −0.37 0.002057 0.000376 930 B3GALT5_P330_F 0.27 0.002067 0.000378 931 TMEFF1_P626_R −0.28 0.002075 0.000379 932 BAX_E281_R −0.25 0.002091 0.000381 933 NPY_P295_F −0.58 0.00217 0.000395 934 VAV2_E58_F −0.19 0.002202 0.000401 935 LMO1_E265_R −0.39 0.002353 0.000427 936 C4B_E171_F −0.29 0.002372 0.00043 937 EPHA8_P456_R 0.34 0.002429 0.00044 938 JAK3_P156_R 0.47 0.002443 0.000443 939 EPHX1_E152_F 0.32 0.002492 0.000451 940 SGCE_P250_R 0.22 0.00251 0.000454 941 HLA-DOB_P1114_R 0.21 0.002513 0.000454 942 LY6G6E_P45_R 0.47 0.002607 0.00047 943 AREG_P217_R 0.21 0.002642 0.000476 944 MAD2L1_E93_F 0.18 0.002966 0.000534 945 ICAM1_E242_F −0.47 0.003073 0.000553 946 IGSF4C_P533_R −0.19 0.003087 0.000554 947 APBA2_P227_F 0.32 0.003154 0.000566 948 CALCA_P171_F 0.28 0.003207 0.000575 949 ER_seq_a1_S60_F −0.42 0.003211 0.000575 950 IL6_P213_R −0.39 0.003248 0.000581 951 KIAA0125_E29_F 0.30 0.00329 0.000588 952 GABRA5_P1016_F −0.41 0.003319 0.000592 953 HLA-DRA_P132_R 0.43 0.003359 0.000599 954 PTGS2_P524_R −0.33 0.003363 0.000599 955 IL12A_E287_R −0.29 0.00346 0.000616 956 PADI4_E24_F 0.39 0.003488 0.00062 957 TIMP3_P1114_R 0.29 0.003578 0.000635 958 AFP_P824_F 0.23 0.003608 0.00064 959 IRAK3_P185_F −0.52 0.003627 0.000643 960 ETV1_P235_F −0.42 0.003651 0.000646 961 INSR_P1063_R 0.48 0.00367 0.000649 962 TNFRSF1A_P678_F 0.25 0.003821 0.000675 963 HTR1B_E232_R −0.44 0.003924 0.000692 964 SH3BP2_P771_R −0.26 0.003943 0.000695 965 S100A4_E315_F 0.46 0.003982 0.000701 966 COL1A2_P48_R 0.70 0.00402 0.000707 967 CDC25B_E83_F −0.51 0.004109 0.000722 968 FGF6_E294_F 0.21 0.004247 0.000745 969 IFNG_P459_R 0.30 0.004346 0.000762 970 LIMK1_P709_R 0.37 0.004364 0.000764 971 IGFBP7_P371_F 0.98 0.004508 0.000789 972 EPHA2_P340_R −0.26 0.004572 0.000799 973 HRASLS_E72_R −0.36 0.004649 0.000812 974 MYH11_P236_R −0.60 0.004771 0.000832 975 TNFRSF10A_P171_F 0.67 0.004859 0.000847 976 PAX6_P50_R −0.55 0.005298 0.000922 977 TFRC_P414_R 0.15 0.00541 0.000941 978 SOX17_P287_R −0.42 0.005558 0.000966 979 ARHGAP9_P518_R 0.25 0.005616 0.000974 980 CD40_E58_R 0.63 0.005617 0.000974 981 MT1A_E13_R 0.52 0.005865 0.001016 982 HSD17B12_E145_R −0.47 0.005973 0.001034 983 GSTM2_P109_R 0.60 0.006015 0.00104 984 MSH3_P13_R 0.26 0.006321 0.001091 985 HIF1A_P488_F −0.24 0.006404 0.001105 986 TAL1_E122_F 0.47 0.006628 0.001142 987 SCGB3A1_E55_R 0.49 0.006879 0.001184 988 GFI1_P45_R −0.47 0.006915 0.001189 989 WNT10B_P823_R 0.43 0.007334 0.00126 990 MUC1_P191_F −0.25 0.007565 0.001298 991 MMP3_P16_R −0.42 0.008058 0.001382 992 ABCB4_P51_F 0.17 0.008165 0.001399 993 IGF2AS_P203_F −0.38 0.00842 0.001441 994 MAPK12_P416_F −0.38 0.008442 0.001443 995 WRN_E57_F −0.21 0.008455 0.001444 996 CDH3_E100_R −0.35 0.008529 0.001455 997 MMP2_P197_F −0.44 0.008857 0.001509 998 SNRPN_E14_F 0.26 0.009036 0.001538 999 CYP1B1_E83_R −0.49 0.009412 0.001601 1000 PROM1_P44_R −0.30 0.00964 0.001638 1001 THY1_P149_R −0.47 0.009649 0.001638 1002 IL8_E118_R −0.25 0.009856 0.001671 1003 DUSP4_E61_F −0.17 0.01003 0.001699 1004 FZD9_E458_F 0.36 0.010176 0.001722 1005 CALCA_E174_R −0.41 0.011 0.00186 1006 IL1RN_E42_F −0.30 0.011457 0.001935 1007 IHH_P529_F −0.32 0.011545 0.001948 1008 ZIM3_E203_F 0.27 0.011986 0.00202 1009 LRRC32_P865_R −0.41 0.012888 0.00217 1010 FGF8_E183_F −0.40 0.013124 0.002206 1011 MAGEL2_E166_R 0.25 0.013127 0.002206 1012 IL11_P11_R −0.40 0.013259 0.002226 1013 LYN_P241_F 0.57 0.013487 0.002262 1014 GABRG3_P75_F −0.30 0.013536 0.002268 1015 ASCL2_P360_F −0.40 0.01355 0.002268 1016 EGR4_P479_F 0.58 0.014415 0.002411 1017 HOXC6_P456_R −0.33 0.014442 0.002413 1018 ONECUT2_P315_R −0.44 0.014785 0.002468 1019 IMPACT_P186_F 0.26 0.014841 0.002475 1020 FZD9_P15_R −0.39 0.015 0.002499 1021 MCAM_P265_R −0.23 0.015581 0.002593 1022 CTGF_P693_R −0.29 0.015598 0.002593 1023 MMP9_P189_F −0.27 0.015637 0.002597 1024 TNFRSF10B_P108_I −0.23 0.016829 0.002792 1025 HLA-DQA2_E93_F 0.23 0.017077 0.002831 1026 HS3ST2_E145_R −0.38 0.017106 0.002833 1027 LMO1_P169_F −0.17 0.017372 0.002874 1028 C4B_P191_F −0.27 0.017475 0.002888 1029 EPHA2_P203_F −0.26 0.018068 0.002984 1030 LIF_E208_F −0.72 0.018828 0.003106 1031 EPHB6_P827_R 0.11 0.019304 0.003181 1032 CSF3R_P8_F −0.28 0.019369 0.003189 1033 PTK2B_P673_R −0.11 0.019498 0.003207 1034 TNC_P198_F 0.19 0.019684 0.003235 1035 ERCC3_P1210_R −0.18 0.019773 0.003246 1036 FLT1_P615_R 0.53 0.020368 0.003341 1037 OSM_P34_F 0.25 0.020403 0.003343 1038 EDN1_P39_R −0.34 0.020531 0.003361 1039 MT1A_P49_R 0.58 0.020731 0.00339 1040 MYLK_E132_R −0.35 0.02106 0.003441 1041 IGF1R_E186_R −0.25 0.021121 0.003448 1042 ACVR1_P983_F 0.33 0.021882 0.003568 1043 CREBBP_P712_R 0.27 0.022723 0.003702 1044 DSG1_E292_F 0.15 0.023665 0.003852 1045 GFI1_E136_F −0.41 0.024198 0.003935 1046 AKT1_P310_R −0.16 0.025402 0.004126 1047 ASCL2_P609_R −0.31 0.026658 0.004326 1048 SNRPN_seq_12_S127_F −0.19 0.027215 0.004412 1049 TRIM29_E189_F −0.27 0.027564 0.004465 1050 AATK_P709_R −0.27 0.027753 0.004491 1051 DIRAS3_P745_F −0.22 0.028093 0.004542 1052 ZNF215_P71_R −0.27 0.028487 0.004601 1053 ARHGDIB_P148_R 0.17 0.02921 0.004714 1054 ELK3_P514_F −0.31 0.029343 0.00473 1055 TAL1_P817_F −0.29 0.029392 0.004734 1056 MAP2K6_P297_R −0.19 0.030268 0.00487 1057 HLA-DOB_E432_R 0.18 0.031387 0.005046 1058 ALOX12_P223_R −0.33 0.031823 0.005111 1059 SNURF_P78_F −0.21 0.032883 0.005276 1060 CDKN2A_E121_R −0.17 0.033582 0.005383 1061 NBL1_E205_R 0.22 0.033754 0.005406 1062 CD2_P68_F 0.29 0.034391 0.005503 1063 NTRK1_E74_F 0.45 0.035783 0.00572 1064 ALK_P28_F −0.38 0.036172 0.005777 1065 IAPP_E280_F −0.23 0.037399 0.005967 1066 DES_P1006_R 0.19 0.037972 0.006053 1067 PTHR1_P258_F 0.19 0.038025 0.006055 1068 MC2R_E455_F 0.35 0.038539 0.006132 1069 MC2R_P1025_F 0.21 0.039187 0.006229 1070 CREB1_P819_F 0.28 0.039628 0.006293 1071 RASSF1_E116_F −0.54 0.039939 0.006337 1072 MST1R_E42_R −0.25 0.04008 0.006353 1073 FER_P581_F 0.29 0.041253 0.006533 1074 PTPRG_E40_R −0.12 0.041291 0.006533 1075 HTR2A_E10_R 0.23 0.041553 0.006568 1076 SOX1_P294_F −0.35 0.042294 0.006679 1077 SEPT5_P441_F −0.23 0.042713 0.006739 1078 TNFSF8_E258_R 0.22 0.043312 0.006823 1079 ARNT_P238_R 0.13 0.043326 0.006823 1080 ASCL1_P747_F −0.25 0.044458 0.006995 1081 CCND1_P343_R −0.22 0.045351 0.007129 1082 EPO_E244_R 0.46 0.046692 0.007329 1083 MKRN3_E144_F 0.30 0.046712 0.007329 1084 DDB2_P407_F −0.20 0.047876 0.007505 1085 TK1_P62_R −0.48 0.048811 0.007644 1086 GRB7_P160_R 0.21 0.051145 0.008002 1087 HOXA9_P303_F −0.24 0.051271 0.008015 1088 WNT1_E157_F −0.34 0.052136 0.008143 1089 GPATC3_P410_R 0.27 0.052585 0.008205 1090 PECAM1_P135_F 0.18 0.052643 0.008207 1091 PTHR1_P170_R 0.19 0.053221 0.008289 1092 LTB4R_E64_R 0.18 0.054156 0.008427 1093 DLC1_P695_F 0.22 0.054933 0.00854 1094 RIPK1_P868_F 0.24 0.055279 0.008586 1095 EGF_E339_F −0.31 0.055534 0.008618 1096 PWCR1_E81_R 0.24 0.055583 0.008618 1097 KRT5_P308_F −0.18 0.055904 0.008659 1098 EMR3_P39_R 0.23 0.055984 0.008664 1099 ATP10A_P147_F −0.24 0.056118 0.008677 1100 NOTCH4_P938_F 0.21 0.056309 0.008699 1101 DNMT2_P199_F 0.13 0.05786 0.00893 1102 LMO2_E148_F 0.24 0.057914 0.00893 1103 HOXA9_E252_R −0.32 0.059186 0.009118 1104 TGFB3_E58_R −0.28 0.060391 0.009295 1105 HIC2_P498_F 0.29 0.061098 0.009396 1106 SHH_E328_F −0.22 0.06232 0.009575 1107 CD40_P372_R 0.34 0.062768 0.009635 1108 CDKN1C_P626_F 0.33 0.06543 0.010035 1109 IL12B_E25_F −0.21 0.06578 0.010079 1110 ITK_E166_R 0.24 0.072329 0.011073 1111 BCL6_P248_R −0.13 0.072425 0.011077 1112 MYB_P673_R −0.25 0.073709 0.011264 1113 ITPR3_E86_R 0.10 0.082578 0.012608 1114 B3GALT5_E246_R −0.21 0.086458 0.013188 1115 MATK_P64_F −0.30 0.086916 0.013246 1116 VAMP8_P114_F 0.26 0.087659 0.013336 1117 TFAP2C_P765_F −0.37 0.087659 0.013336 1118 PSCA_E359_F 0.19 0.092195 0.014013 1119 MEG3_E91_F −0.15 0.093166 0.014148 1120 RIPK3_P124_F 0.24 0.093679 0.014213 1121 RYK_P493_F 0.15 0.096451 0.014621 1122 HLA-DOA_P594_F −0.13 0.097533 0.014771 1123 PYCARD_P150_F 0.14 0.099792 0.0151 1124 TAL1_P594_F −0.27 0.100215 0.015151 1125 CYP1A1_P382_F −0.16 0.100332 0.015155 1126 POMC_E254_F −0.24 0.100589 0.01518 1127 COL1A2_E299_F 0.40 0.100752 0.015191 1128 PLSCR3_P751_R 0.16 0.100899 0.0152 1129 ZP3_E90_F 0.40 0.102223 0.015386 1130 TIE1_E66_R −0.17 0.103277 0.015531 1131 EVI2A_E420_F 0.19 0.105022 0.015779 1132 S100A2_P1186_F 0.20 0.105563 0.015847 1133 TEK_P526_F −0.14 0.106105 0.015914 1134 NR2F6_E375_R 0.06 0.113337 0.016984 1135 HDAC7A_P344_F 0.21 0.11431 0.017114 1136 IHH_E186_F −0.30 0.114459 0.017121 1137 HLA-DRA_P77_R 0.22 0.115053 0.017181 1138 PADI4_P1158_R 0.18 0.115057 0.017181 1139 FGFR3_P1152_R −0.19 0.115865 0.017286 1140 DNMT3B_P352_R −0.16 0.116786 0.017408 1141 GNAS_E58_F 0.14 0.117162 0.017449 1142 C20orf47_P225_R −0.07 0.117316 0.017457 1143 SIN3B_P514_R −0.20 0.117758 0.017507 1144 PI3_P274_R 0.18 0.118691 0.01763 1145 HDAC9_E38_F 0.26 0.120161 0.017833 1146 TNFRSF1B_P167_F −0.27 0.120373 0.017849 1147 ACTG2_E98_R 0.17 0.120626 0.017871 1148 PGF_E33_F 0.27 0.120855 0.017889 1149 SMAD2_P848_R −0.15 0.123708 0.018296 1150 COL4A3_E205_R −0.14 0.124659 0.01842 1151 PENK_E26_F 0.22 0.124919 0.018443 1152 ITPR2_P804_F −0.14 0.133578 0.019704 1153 SMARCA3_E20_F −0.14 0.13379 0.019718 1154 SLC14A1_P369_R 0.20 0.135114 0.019896 1155 SGCE_E149_F −0.24 0.136794 0.020126 1156 LTA_E28_R 0.23 0.138226 0.020319 1157 CPA4_E20_F −0.13 0.138926 0.020405 1158 EVI2A_P94_R −0.23 0.142096 0.020852 1159 MAPK4_E273_R −0.15 0.14225 0.020857 1160 PTK2_P735_R 0.22 0.142813 0.020921 1161 TSP50_P137_F −0.22 0.143467 0.020999 1162 STAT5A_P704_R 0.15 0.144191 0.021087 1163 IFNG_P188_F 0.17 0.148996 0.021771 1164 IL4_P262_R 0.09 0.149813 0.021871 1165 CCNC_P132_R −0.22 0.152705 0.022275 1166 CSF1R_P73_F 0.11 0.155802 0.022707 1167 MMP3_P55_F 0.15 0.15834 0.023057 1168 CHGA_E52_F −0.23 0.160067 0.02328 1169 RHOH_P121_F 0.17 0.160143 0.02328 1170 MYBL2_P211_F 0.47 0.162983 0.023672 1171 TDGF1_P428_R −0.12 0.163849 0.023778 1172 GLI2_E90_F 0.21 0.165669 0.024021 1173 MMP2_P303_R −0.24 0.165915 0.024037 1174 GSTM2_P453_R 0.16 0.167055 0.024181 1175 SNURF_E256_R 0.11 0.167483 0.024222 1176 RAD50_P191_F −0.14 0.170197 0.024569 1177 SIN3B_P607_F −0.09 0.170286 0.024569 1178 RBP1_P426_R 0.26 0.170312 0.024569 1179 TFF2_P178_F −0.17 0.171813 0.024764 1180 ZIM2_E110_F −0.11 0.17351 0.024988 1181 SLC5A5_E60_F 0.17 0.174137 0.025057 1182 RUNX3_P393_R 0.17 0.177486 0.025517 1183 IL10_P348_F 0.09 0.180037 0.025862 1184 LRRC32_E157_F −0.11 0.180634 0.025926 1185 FAS_P65_F −0.08 0.181466 0.026023 1186 XPC_P226_R 0.07 0.182697 0.026178 1187 EMR3_E61_F 0.17 0.18425 0.026378 1188 APOA1_P75_F −0.22 0.18576 0.026572 1189 PITX2_P183_R 0.14 0.186706 0.026685 1190 ATP10A_P524_R −0.15 0.18736 0.026756 1191 MPO_E302_R 0.15 0.188557 0.026904 1192 TNFRSF10C_P612_I 0.08 0.189503 0.027016 1193 MLLT4_P1400_F 0.31 0.190011 0.027066 1194 TES_E172_F −0.25 0.191889 0.027311 1195 IGFBP1_P12_R 0.19 0.193424 0.027506 1196 H19_P541_F 0.21 0.194485 0.027634 1197 ICAM1_P386_R −0.28 0.208835 0.029648 1198 IGFBP2_P353_R −0.16 0.212437 0.030135 1199 APBA1_E99_R 0.11 0.214037 0.030336 1200 RET_P717_F −0.14 0.216943 0.030722 1201 MATK_P190_R −0.17 0.21791 0.030834 1202 KCNK4_E3_F −0.14 0.218833 0.030916 1203 EYA4_P508_F 0.19 0.218881 0.030916 1204 RIPK4_E166_F −0.14 0.21904 0.030916 1205 NFKB1_P336_R −0.21 0.225726 0.031834 1206 PTPN6_E171_R −0.19 0.227674 0.032082 1207 PMP22_P1254_F 0.08 0.228272 0.032126 1208 TFPI2_E141_F 0.09 0.228363 0.032126 1209 RASGRF1_P768_F 0.19 0.229233 0.032221 1210 SEPT5_P464_R −0.13 0.229456 0.032226 1211 AXL_E61_F −0.15 0.230742 0.03238 1212 MSH3_E3_F −0.18 0.234379 0.032857 1213 CDKN2B_E220_F −0.09 0.234527 0.032857 1214 EGF_P242_R 0.13 0.235829 0.033012 1215 ZIM3_P718_R −0.16 0.237428 0.033209 1216 NOTCH4_E4_F 0.18 0.24965 0.034889 1217 TFPI2_P152_R −0.08 0.251819 0.035164 1218 TERT_E20_F 0.15 0.25534 0.035626 1219 AATK_P519_R −0.14 0.257898 0.035953 1220 PDGFRA_E125_F 0.16 0.263562 0.036713 1221 IGFBP1_E48_R 0.17 0.263808 0.036717 1222 ZAP70_P220_R 0.11 0.265491 0.036921 1223 SHB_P691_R −0.18 0.265958 0.036956 1224 BLK_P668_R 0.09 0.273799 0.038014 1225 MYBL2_P354_F −0.20 0.274753 0.038116 1226 DIRAS3_E55_R 0.11 0.27786 0.038515 1227 MET_E333_F −0.12 0.278411 0.03856 1228 ABCB4_P892_F 0.17 0.281453 0.03895 1229 TFAP2C_E260_F 0.09 0.294381 0.040706 1230 GP1BB_P278_R 0.15 0.294853 0.040738 1231 CDK6_E256_F 0.05 0.296769 0.040942 1232 ESR1_E298_R 0.22 0.296812 0.040942 1233 IRAK3_P13_F −0.34 0.2972 0.040963 1234 HOXA11_E35_F −0.17 0.298247 0.041073 1235 JAK3_E64_F 0.20 0.300751 0.041385 1236 RAP1A_P285_R −0.11 0.301149 0.041406 1237 ABCB4_E429_F 0.07 0.3021 0.041503 1238 CPA4_P1265_R 0.05 0.302375 0.041508 1239 SPDEF_P6_R 0.11 0.302668 0.041514 1240 FGF1_P357_R −0.14 0.306003 0.041938 1241 HIC2_P528_R 0.16 0.306432 0.041953 1242 GFI1_P208_R 0.17 0.306605 0.041953 1243 TRIM29_P135_F −0.11 0.309249 0.042281 1244 PTPRO_P371_F −0.13 0.315795 0.043141 1245 PTPN6_P282_R −0.12 0.319551 0.043619 1246 MAPK10_E26_F −0.15 0.322553 0.043993 1247 EPHX1_P22_F 0.12 0.323301 0.04406 1248 CASP2_P192_F −0.20 0.330236 0.044969 1249 SOX2_P546_F 0.20 0.332391 0.045226 1250 GSTM1_P266_F −0.12 0.332764 0.045241 1251 HOXA5_P479_F −0.11 0.334259 0.045408 1252 NRAS_P12_R −0.06 0.334557 0.045412 1253 BMP2_P1201_F −0.09 0.339666 0.046069 1254 GUCY2D_E419_R −0.24 0.345755 0.046857 1255 CCL3_E53_R −0.12 0.346989 0.04698 1256 ACVR1_E328_R 0.15 0.34721 0.04698 1257 ERBB2_P59_R 0.07 0.349446 0.047209 1258 LTB4R_P163_F −0.07 0.349461 0.047209 1259 ALOX12_E85_R −0.15 0.349808 0.047218 1260 NPY_P91_F −0.18 0.351668 0.047432 1261 MST1R_P392_F −0.19 0.356138 0.047997 1262 ASCL1_E24_F −0.12 0.361401 0.048668 1263 GP1BB_E23_F −0.14 0.365483 0.049178 1264 NGFR_P355_F 0.12 0.366627 0.049293 1265 CD44_E26_F −0.19 0.371126 0.049859 1266

SUPPLEMENTAL TABLE 8 CpG loci with differential methylation between normal and tumorigenic head and neck tissues. Regression GENE_CpG coefficient* P-value Q-value Rank ERBB2_P59_R 0.96 0 0 1 HOXA9_P1141_R −2.06 0 3.00E−06 2 CASP8_E474_F 1.21 0 1.60E−05 3 ERN1_P809_R 1.14 0 2.80E−05 4 ICAM1_P386_R 1.48 0 4.00E−05 5 RIPK1_P744_R −0.89 2.00E−06 0.000196 6 HOXA5_P1324_F −1.28 1.10E−05 0.000822 7 RAB32_P493_R 1.08 1.90E−05 0.001206 8 DLC1_P695_F 1.08 2.70E−05 0.001307 9 HBII-52_E142_F 0.98 2.90E−05 0.001307 10 HTR1B_E232_R −1.35 2.90E−05 0.001307 11 CCL3_E53_R 1.07 3.30E−05 0.001391 12 HOXA9_E252_R −1.51 4.20E−05 0.001609 13 HOXA11_P698_F −1.44 4.50E−05 0.001609 14 HS3ST2_E145_R −1.63 5.00E−05 0.001666 15 PENK_E26_F −1.58 5.60E−05 0.001668 16 RUNX3_E27_R 1.44 5.60E−05 0.001668 17 GP1BB_P278_R 1.21 8.90E−05 0.002361 18 HLA-DPB1_E2_R 1.00 9.10E−05 0.002361 19 TERT_P360_R −1.90 9.40E−05 0.002361 20 VAMP8_E7_F 0.78 0.000108 0.002473 21 PTPRH_E173_F 1.00 0.000108 0.002473 22 ADCYAP1_P398_F −1.80 0.000115 0.002473 23 MME_P388_F −1.68 0.00012 0.002473 24 GP1BB_E23_F 1.13 0.000123 0.002473 25 ITK_P114_F 1.31 0.000135 0.002614 26 AIM2_P624_F 1.57 0.000155 0.00289 27 HTR1B_P107_F −1.45 0.000167 0.002994 28 NPY_E31_R −1.36 0.000177 0.003005 29 SEMA3C_P642_F 1.11 0.000184 0.003005 30 PRSS1_P1249_R 1.03 0.000185 0.003005 31 HTR1B_P222_F −1.92 0.000201 0.003159 32 GDF10_E39_F −0.87 0.000208 0.003173 33 VAMP8_P114_F 1.02 0.00022 0.003197 34 CCL3_P543_R 0.84 0.000223 0.003197 35 MOS_E60_R −1.49 0.000229 0.003197 36 SHH_E328_F −1.10 0.000244 0.003325 37 RIPK1_P868_F −1.03 0.000288 0.003797 38 DCC_P471_R −1.61 0.000294 0.003797 39 MLF1_E243_F −1.43 0.000303 0.003814 40 WNT8B_E487_F 0.90 0.000317 0.003888 41 IFNG_E293_F 0.81 0.000366 0.004387 42 IL10_P85_F 1.04 0.000386 0.004517 43 DLK1_E227_R −1.75 0.000398 0.004553 44 CEACAM1_E57_R 0.72 0.000458 0.005123 45 TNFSF8_P184_F 1.05 0.000521 0.0057 46 OSM_P34_F 1.18 0.000577 0.006187 47 HS3ST2_P171_F −2.04 0.000591 0.006202 48 EPHA5_P66_F −0.89 0.000658 0.006764 49 PLA2G2A_P528_F 0.98 0.000689 0.006913 50 ABL2_P459_R 0.40 7.00E−04 0.006913 51 ADCYAP1_P455_R −2.12 0.000743 0.007197 52 AOC3_P890_R 0.78 0.000785 0.007371 53 MT1A_E13_R −1.50 0.000791 0.007371 54 HS3ST2_P546_F −1.24 0.000828 0.007577 55 MYOD1_E156_F −1.56 0.000844 0.007586 56 EMR3_P39_R 0.88 0.000905 0.007996 57 CDH1_P45_F 0.59 0.000936 0.008126 58 OSM_P188_F 1.41 0.000958 0.00816 59 HOXB2_P99_F −0.69 0.000972 0.00816 60 H19_P1411_R 0.96 0.00103 0.008504 61 NPY_P295_F −1.62 0.001062 0.008626 62 RUNX3_P393_R 1.21 0.001106 0.008839 63 PENK_P447_R −1.41 0.001161 0.009137 64 ATP10A_P524_R 0.80 0.001244 0.009633 65 EYA4_E277_F −1.49 0.001278 0.009749 66 TIAM1_P188_R 0.61 0.001303 0.00979 67 SOX1_P1018_R −1.67 0.00136 0.010069 68 TAL1_P594_F −0.96 0.001414 0.010318 69 MPO_P883_R 0.85 0.001615 0.011246 70 ICAM1_P119_R 0.30 0.00162 0.011246 71 CALCA_E174_R −1.15 0.001644 0.011246 72 DBC1_P351_R −1.52 0.001649 0.011246 73 CD2_P68_F 1.03 0.001653 0.011246 74 TNFSF8_E258_R 1.26 0.001701 0.011418 75 GABRA5_P862_R 1.25 0.00173 0.01146 76 EMR3_E61_F 0.67 0.00178 0.011553 77 CHGA_E52_F −1.40 0.001805 0.011553 78 CDKN1B_P1161_F −1.82 0.001839 0.011553 79 HHIP_P578_R −1.26 0.00187 0.011553 80 TGFB3_E58_R −0.85 0.001884 0.011553 81 HDAC1_P414_R 0.71 0.001911 0.011553 82 HLA-DPA1_P205_R 0.81 0.001922 0.011553 83 EPHA3_P106_R −1.72 0.001927 0.011553 84 CTLA4_P1128_F 0.58 0.002182 0.012925 85 SOX17_P303_F −1.18 0.002267 0.013196 86 BLK_P14_F 0.92 0.00228 0.013196 87 BDNF_P259_R −0.95 0.0024 0.013731 88 CASP10_E139_F 0.79 0.002455 0.013891 89 SOX1_P294_F −1.48 0.002489 0.013926 90 MPO_E302_R 1.05 0.002592 0.014341 91 ELL_P693_F 0.60 0.002627 0.014377 92 VAV1_P317_F 0.82 0.002704 0.014638 93 MAP3K1_E81_F −1.39 0.002923 0.015564 94 DIO3_E230_R −0.72 0.002936 0.015564 95 EYA4_P508_F −1.41 0.003028 0.01588 96 COL1A1_P5_F −1.00 0.003067 0.015923 97 PTHLH_E251_F 0.77 0.003204 0.01646 98 IGF2AS_P203_F −0.94 0.003274 0.01665 99 GFI1_P208_R 0.92 0.003346 0.016847 100 USP29_E274_F 1.05 0.003388 0.016892 101 GSTM1_P266_F −0.78 0.003491 0.017112 102 DCC_E53_R −0.74 0.0035 0.017112 103 OGG1_E400_F −0.93 0.003616 0.017507 104 DBC1_E204_F −1.08 0.003712 0.017802 105 AFF3_P122_F 1.11 0.003798 0.018041 106 MMP8_E89_R 0.58 0.003951 0.018591 107 GABRB3_P92_F −0.87 0.004188 0.019523 108 CD34_E20_R −0.55 0.004257 0.019666 109 AGXT_P180_F 1.30 0.004441 0.020301 110 SLC5A8_E60_R −0.95 0.004509 0.020301 111 CD9_P585_R −0.76 0.004531 0.020301 112 TRPM5_E87_F 1.05 0.004556 0.020301 113 GNAS_P86_F 0.58 0.004862 0.021475 114 RUNX3_P247_F 1.21 0.00507 0.021849 115 APBA2_P305_R 0.78 0.005077 0.021849 116 KLK10_P268_R 0.37 0.005118 0.021849 117 NTRK3_P636_R −1.91 0.00512 0.021849 118 GML_P281_R 1.36 0.005266 0.022282 119 CALCA_P75_F −1.26 0.005315 0.022303 120 TNFRSF10A_P171_F 0.62 0.005497 0.022877 121 CD9_P504_F −0.88 0.005552 0.022914 122 AGTR1_P41_F −2.07 0.005695 0.023312 123 MAPK4_E273_R 0.77 0.005816 0.023609 124 PI3_P1394_R 0.67 0.005861 0.023609 125 ITGA6_P298_R −1.59 0.005981 0.023903 126 GABRA5_P1016_F 0.96 0.006101 0.024188 127 LTA_P214_R 1.04 0.0062 0.024391 128 CDKN2B_seq_50_S29 −1.37 0.0063 0.024484 129 TPEF_seq_44_S88_R −1.46 0.006385 0.024484 130 SEMA3B_E96_F −0.75 0.006461 0.024484 131 MEST_P62_R 0.66 0.006482 0.024484 132 FLJ20712_P984_R 0.84 0.0066 0.024484 133 PROM1_P44_R 1.05 0.006681 0.024484 134 SPP1_P647_F 0.82 0.006685 0.024484 135 SPI1_E205_F 0.52 0.006739 0.024484 136 WT1_E32_F −1.56 0.006756 0.024484 137 WNT10B_P823_R 0.75 0.006793 0.024484 138 PMP22_P975_F 1.04 0.006805 0.024484 139 PWCR1_P357_F 0.72 0.006808 0.024484 140 HOXB13_E21_F −1.18 0.006919 0.02455 141 IFNG_P459_R 0.69 0.006968 0.02455 142 CALCA_P171_F −0.58 0.006986 0.02455 143 NEFL_E23_R −1.07 0.007061 0.02455 144 EPHA5_E158_R −1.82 0.00707 0.02455 145 ABCB4_P892_F 0.83 0.007241 0.024639 146 SPARC_P195_F −1.13 0.00725 0.024639 147 EMR3_P1297_R 0.97 0.007252 0.024639 148 SERPINE1_E189_R −0.71 0.007295 0.024639 149 PGR_P790_F 0.77 0.00734 0.024639 150 ADCYAP1_E163_R −1.27 0.007843 0.026014 151 GALR1_E52_F −1.81 0.007853 0.026014 152 PI3_E107_F 1.12 0.008082 0.026436 153 CYP1B1_E83_R −1.61 0.008171 0.026436 154 CDK10_E74_F −0.88 0.008172 0.026436 155 DCC_P177_F −1.18 0.008233 0.026436 156 FN1_P229_R −0.49 0.008251 0.026436 157 EVI2A_P94_R 1.12 0.008295 0.026436 158 NFKB2_P709_R −1.41 0.008398 0.026596 159 INS_P248_F 0.81 0.008522 0.026805 160 MT1A_P49_R −1.82 0.008571 0.026805 161 WNT5A_P655_F −1.67 0.008659 0.026913 162 HLA-DPA1_E35_R 0.59 0.008948 0.02764 163 EDNRB_P709_R 1.09 0.009033 0.027734 164 TFRC_P414_R −0.73 0.009208 0.028101 165 MKRN3_E144_F 1.14 0.009282 0.028154 166 NTRK2_P395_R −1.74 0.009463 0.028474 167 EGF_P413_F 0.87 0.0095 0.028474 168 ITK_E166_R 1.41 0.009727 0.028981 169 GPR116_P850_F 0.55 0.009826 0.029104 170 CD1A_P414_R 0.46 0.009926 0.029227 171 CSF2_E248_R 0.86 0.010229 0.029944 172 CEACAM1_P44_R 0.62 0.010357 0.030144 173 TBX1_P885_R 0.93 0.010431 0.030184 174 SLC14A1_E295_F 0.74 0.010888 0.031003 175 H19_P541_F 0.74 0.010888 0.031003 176 FRZB_E186_R −0.94 0.010916 0.031003 177 THPO_E483_F 0.67 0.010994 0.031003 178 TCF7L2_P193_R −1.06 0.011021 0.031003 179 CRIP1_P874_R 0.55 0.011111 0.031082 180 APOC1_P406_R 0.52 0.011298 0.031403 181 SFTPB_P689_R 0.74 0.011351 0.031403 182 LAT_E46_F 0.90 0.01151 0.03167 183 HOXA5_P479_F −0.62 0.011821 0.032348 184 SLC22A18_P216_R −0.59 0.011895 0.032376 185 INS_P804_R 1.27 0.012126 0.032827 186 HIF1A_P488_F −1.18 0.012326 0.033189 187 TIE1_E66_R 0.76 0.012568 0.033483 188 IGFBP5_E144_F −0.90 0.012568 0.033483 189 AGTR1_P154_F −1.23 0.012721 0.033713 190 TMEM63A_E63_F 0.31 0.012952 0.034048 191 TMEFF2_P152_R −0.98 0.013015 0.034048 192 SFTPA1_E340_R 1.45 0.013083 0.034048 193 SLC22A3_P634_F 0.67 0.013177 0.034048 194 ABCB4_P51_F 0.67 0.013186 0.034048 195 PWCR1_P811_F 0.83 0.01357 0.034861 196 MYBL2_P211_F 0.31 0.013796 0.035261 197 PWCR1_E81_R 0.90 0.013967 0.035518 198 CARD15_P665_F 0.75 0.014317 0.036018 199 MMP1_P460_F 0.44 0.014322 0.036018 200 SPARC_E50_R −0.81 0.014387 0.036018 201 EDNRB_P148_R 0.96 0.014449 0.036018 202 LCK_E28_F 1.04 0.014627 0.036263 203 ABCB4_E429_F 0.70 0.014746 0.036263 204 GDF10_P95_R −1.05 0.014939 0.036263 205 TSG101_P257_R −0.72 0.014947 0.036263 206 IPF1_P750_F −0.71 0.015082 0.036263 207 VAV1_E9_F 0.68 0.015124 0.036263 208 FLT4_E206_F −0.63 0.015129 0.036263 209 APBA2_P227_F 0.61 0.015185 0.036263 210 HLA-DQA2_E93_F 0.59 0.015285 0.036263 211 MPL_P657_F 0.65 0.015319 0.036263 212 NQO1_P345_R −1.14 0.01534 0.036263 213 RYK_P493_F −1.13 0.015654 0.036834 214 PPAT_E170_R 0.44 0.016381 0.03835 215 TNFRSF1B_E5_F 0.59 0.016451 0.03835 216 NOTCH4_P938_F 0.60 0.016857 0.03895 217 TESK2_P252_R −0.96 0.016863 0.03895 218 NQO1_E74_R −0.80 0.017109 0.039337 219 LAMC1_P808_F −0.93 0.017265 0.039515 220 NTRK3_P752_F −1.64 0.017478 0.039755 221 SFN_P248_F 0.43 0.017528 0.039755 222 NPY_P91_F −1.58 0.017619 0.03977 223 YES1_P600_F −1.01 0.017692 0.03977 224 PADI4_E24_F 1.04 0.017883 0.040019 225 FGF12_P210_R −1.41 0.018052 0.040052 226 ST6GAL1_P528_F −1.36 0.018056 0.040052 227 BLK_P668_R 1.02 0.018209 0.040164 228 PSCA_E359_F 0.66 0.018267 0.040164 229 ZAP70_P220_R 0.72 0.018518 0.040539 230 SLC5A8_P38_R −1.16 0.018618 0.040583 231 IL13_E75_R 0.67 0.01881 0.040825 232 PGR_P456_R 0.82 0.019038 0.040989 233 CCR5_P630_R 0.48 0.019049 0.040989 234 NOTCH3_E403_F −0.96 0.019465 0.041707 235 CFTR_P372_R −0.79 0.020007 0.042685 236 DDIT3_P1313_R −0.68 0.020161 0.042833 237 FGF12_E61_R −1.14 0.020559 0.043496 238 FGF9_P862_R −0.20 0.020778 0.043776 239 IL12B_P392_R 0.86 0.021269 0.044623 240 KRT1_P798_R 0.56 0.021667 0.045029 241 THBS2_E129_F −1.17 0.021713 0.045029 242 SNRPN_seq_18_S99_F 0.49 0.021731 0.045029 243 PLXDC2_P914_R −1.05 0.022106 0.045437 244 MOS_P27_R −1.06 0.022122 0.045437 245 IRF5_E101_F −0.56 0.022199 0.045437 246 ACVR1B_P572_R −0.59 0.02248 0.045712 247 HGF_E102_R −0.89 0.022558 0.045712 248 RASGRF1_E16_F −2.36 0.022605 0.045712 249 MAP2K6_E297_F −0.99 0.022876 0.046075 250 KDR_P445_R −1.55 0.023314 0.04677 251 TBX1_P520_F 0.57 0.023494 0.046943 252 GJB2_P931_R 0.60 0.023718 0.047172 253 VAMP8_P241_F 0.54 0.023796 0.047172 254 HOXA9_P303_F −0.83 0.023962 0.047315 255 HLA-DPB1_P540_F 0.43 0.02463 0.048063 256 IHH_E186_F −1.34 0.024632 0.048063 257 SEPT9_P58_R −0.64 0.024653 0.048063 258 SOX17_P287_R −0.76 0.024722 0.048063 259 NES_P239_R −0.62 0.024919 0.048259 260 FANCG_E207_R −0.77 0.025799 0.049771 261 *Positive value indicates increased methylation in normal head and neck tissues relative to tumors

SUPPLEMENTAL TABLE 9 Logistic regression model of tumor stage by methylation class membership; Head and neck squamous cell carcinoma. Stage 1 or Stage 3 or Methylation Class 2, n (%) 4, n (%) OR (95% CI) P Class 1 2 (17%) 10 (83%) Referent Class 2  l (50%)  1 (50%) 0.05 (0.001, 2.9) 0.15 Class 3 0 (0%)  1 (100%) ND ND Class 4 3 (100%)  0 (0%) ND ND Class 5 2 (12%) 15 (88%) 3.0 (0.2, 57.9) 0.4 Class 6 6 (50%)  6 (50%) 0.1 (0.01, 1.0) 0.05 Note: Logistic regression for high stage (III or IV) compared to low stage (I or II) controlled for age and gender.

SUPPLEMENTAL TABLE 10 Loci with methylation beta values significantly associated with patient survival in head and neck squamous cell carcinoma (FDR Q-value < 0.2) Hazard Gene Locus Ratio P-value Q-value HGF-E102 4.01E−04 2.10E−04 0.08 ATP10A-P524 3.91E−04 4.00E−04 0.08 SEMA3A-P343 1.23E−03 1.60E−03 0.15 NTRK3-E131 7.48E−06 1.80E−03 0.15 ZAP7O-P220 5.98E+02 2.20E−03 0.15 GP1BB-P278 5.51E+01 2.70E−03 0.15 OPCML-E219 3.68E−03 2.80E−03 0.15 MME-P388 2.71E−02 3.50E−03 0.15 FGF5-P238 1.89E−04 3.70E−03 0.15 UBA52-P293 6.29E−03 4.10E−03 0.15 MC2R-P1025 6.39E−03 4.10E−03 0.15 CDH11-P354 1.22E−02 4.50E−03 0.16 TMEFF2-P152 7.38E−03 4.90E−03 0.16 FLI1-E29 2.33E−04 6.10E−03 0.18 NES-P239 2.83E−03 6.90E−03 0.18 DAPK1-P10 8.43E−04 7.10E−03 0.18 NEFL-P209 5.78E−03 8.20E−03 0.2 ASCL1-P747 1.72E−02 8.60E−03 0.2

SUPPLEMENTAL TABLE 11 CpG loci which best differentiate RPMM methylation class 3 (exclusively normal bladder samples) relative to other RPMM classes (comprised of bladder tumors). GENE_CpG AUC - Class 3 compared to Others CEACAM1_E57_R 1.000 IGF2R_P396_R 1.000 HPSE_P29_F 1.000 MLH3_P25_F 1.000 MLF1_P97_F 1.000 COL6A1_P425_F 1.000 CASP8_E474_F 1.000 NPR2_P1093_F 1.000 EPHB4_E476_R 1.000 FGFR2_P460_R 1.000 LAMB1_E144_R 1.000 TJP2_P518_F 1.000 VAMP8_P114_F 1.000 TRAF4_P372_F 1.000 IGSF4C_E65_F 1.000 SFN_P248_F 1.000 IGF1R_P325_R 1.000 KCNQ1_E349_R 1.000 INSR_E97_F 1.000 DST_P262_R 1.000 HPSE_P93_F 1.000 ABCG2_P178_R 1.000 MUC1_E18_R 1.000 MCM2_P260_F 1.000 ERCC6_P698_R 1.000 CEACAM1_P44_R 0.999 NOTCH3_P198_R 0.999 ABL2_P459_R 0.999 INHA_P1144_R 0.999 EPHA3_P106_R 0.999 TNFRSF10A_P91_F 0.999 PTPRH_E173_F 0.999 HDAC1_P414_R 0.999 ACVR1C_P115_R 0.999 FER_P581_F 0.999 TK1_P62_R 0.999 NBL1_P24_F 0.999 PTK6_E50_F 0.999 PCDH1_E22_F 0.999 TRIM29_P261_F 0.998 DHCR24_P406_R 0.998 PTHR1_P258_F 0.998 RARRES1_P57_R 0.998 FER_E119_F 0.998 MYCN_E77_R 0.998 PHLDA2_P622_F 0.998 KRAS_P651_F 0.998 TJP2_P330_R 0.998 PPARD_P846_F 0.998 RIPK3_P124_F 0.998 IGFBP1_P12_R 0.997 NOS3_P38_F 0.997 MMP7_E59_F 0.997 ENC1_P484_R 0.997 ITGB4_E144_F 0.997 S100A2_P1186_F 0.996 PAX6_E129_F 0.996 COPG2_P298_F 0.996 MLF1_E243_F 0.996 TNFSF10_E53_F 0.996 CTNNA1_P382_R 0.996 TGFB2_P632_F 0.995 IL1B_P829_F 0.995 PTPN6_P282_R 0.995 VAMP8_E7_F 0.995 RASA1_E107_F 0.995 MCM2_P241_R 0.995 WNT2B_P1185_R 0.994 EIF2AK2_E103_R 0.994 IL1RN_E42_F 0.994 PLXDC1_E71_F 0.993 ID1_P880_F 0.993 MATK_P190_R 0.993 BCAM_P205_F 0.993 BAX_E281_R 0.992 SHB_P691_R 0.992 PCGF4_P760_R 0.992 MYLK_E132_R 0.992 TRIM29_E189_F 0.991 EMR3_P39_R 0.991 TFAP2C_P765_F 0.991 PENK_P447_R 0.991 NPR2_P618_F 0.991 DDR1_P332_R 0.990 TNFRSF10A_P171_F 0.990 CPA4_P961_R 0.990 STK11_P295_R 0.990 ICAM1_P119_R 0.989 DDB2_P407_F 0.989 TAL1_P594_F 0.989 SERPINB5_P19_R 0.989 TUBB3_E91_F 0.989 EMR3_E61_F 0.989 NTRK2_P395_R 0.988 SPDEF_P6_R 0.988 COL4A3_P545_F 0.988 IL8_P83_F 0.987 MAP3K1_P7_F 0.987 DSP_P36_F 0.987 AIM2_E208_F 0.986 CASP6_P230_R 0.986 GNMT_E126_F 0.986 THY1_P20_R 0.986 CSF3_P309_R 0.986 TFF2_P178_F 0.986 MMP10_E136_R 0.985 GSTM1_P266_F 0.984 EPS8_E231_F 0.984 DDR1_E23_R 0.983 NBL1_E205_R 0.983 APP_E8_F 0.983 SPDEF_E116_R 0.983 CAPG_E228_F 0.982 IPF1_P750_F 0.982 EPHB2_E297_F 0.982 CDH3_P87_R 0.981 MGMT_P272_R 0.981 EPHA2_P340_R 0.980 DLK1_E227_R 0.980 CYP1B1_E83_R 0.980 CDKN2B_seq_50_S294_F 0.980 SOX1_P1018_R 0.980 HLA-DPA1_P205_R 0.980 HBII-13_P991_R 0.979 SYK_E372_F 0.979 MME_P388_F 0.979 SRC_E100_R 0.978 VAMP8_P241_F 0.978 RYK_P493_F 0.978 IGF2AS_P203_F 0.978 RHOH_P121_F 0.978 CXCL9_E268_R 0.978 IFNG_E293_F 0.978 TFAP2C_E260_F 0.977 PTGS1_E80_F 0.977 WNT2B_P1195_F 0.976 VAV1_E9_F 0.976 TRIM29_P135_F 0.975 HOXA9_E252_R 0.975 FGFR3_E297_R 0.974 PDGFB_E25_R 0.974 P2RX7_P597_F 0.974 PSCA_E359_F 0.973 HDAC5_E298_F 0.973 CLDN4_P1120_R 0.973 ITGA2_E120_F 0.973 HOXA9_P1141_R 0.972 HIC-1_seq_48_S103_R 0.972 SLC14A1_E295_F 0.972 HOXA9_P303_F 0.972 BCL3_E71_F 0.971 PTCH_E42_F 0.971 APOC1_P406_R 0.971 NID1_P677_F 0.971 CRK_P721_F 0.969 MMP9_P237_R 0.969 HLA-DOB_E432_R 0.969 JAG1_P66_F 0.969 ITGB1_P451_F 0.968 FN1_P229_R 0.968 PI3_E107_F 0.968 FGFR2_P266_R 0.967 TMPRSS4_E83_F 0.967 PTPN6_E171_R 0.966 MMP14_P208_R 0.966 CCR5_P630_R 0.966 FRK_P258_F 0.965 ER_seq_a1_S60_F 0.964 IL18BP_E285_F 0.964 SFN_E118_F 0.964 INHA_P1189_F 0.964 NOS2A_E117_R 0.964 IFNGR1_P307_F 0.962 PTK7_E317_F 0.962 CDH17_P376_F 0.961 PRKAR1A_P337_R 0.961 MCC_P196_R 0.961 CDKN1B_P1161_F 0.961 HS3ST2_E145_R 0.960 CD9_E14_R 0.960 FRK_P36_F 0.959 RBP1_P426_R 0.959 CARD15_P302_R 0.959 TRIP6_P1090_F 0.959 SPP1_P647_F 0.959 RARB_P60_F 0.959 MYCN_P464_R 0.958 JAK3_P1075_R 0.958 FGFR3_P1152_R 0.958 B3GALT5_P330_F 0.957 FLJ20712_P984_R 0.957 MYBL2_P354_F 0.957 BMPR2_E435_F 0.957 PI3_P274_R 0.956 LIG3_P622_R 0.956 MBD2_P233_F 0.956 ITGB4_P517_F 0.956 CDH3_E100_R 0.955 INSR_P1063_R 0.955 SNCG_P98_R 0.955 MLH3_E72_F 0.954 BCR_P422_F 0.954 PYCARD_P150_F 0.954 EGR4_E70_F 0.954 TFDP1_P543_R 0.953 SFTPA1_E340_R 0.953 CTSH_P238_F 0.952 CTSD_P726_F 0.951 IL1RN_P93_R 0.951 ACVR1B_E497_R 0.951 PTPRH_P255_F 0.951 CPNE1_P138_F 0.951 ICA1_P61_F 0.951 IGFBP3_E65_R 0.950 SEMA3F_P692_R 0.948 KIAA1804_P689_R 0.948 AATK_E63_R 0.948 TUSC3_P85_R 0.947 EGF_P413_F 0.947 TIAM1_P117_F 0.946 RIPK4_E166_F 0.946 PHLDA2_E159_R 0.946 GABRA5_P1016_F 0.946 TJP1_P326_R 0.945 GAS1_P754_R 0.944 BMP3_P56_R 0.944 MST1R_E42_R 0.944 GATA6_P21_R 0.944 TFF1_P180_R 0.943 GSTM1_P363_F 0.943 APBA2_P305_R 0.943 THBS2_P605_R 0.942 WNT5A_P655_F 0.942 TWIST1_P355_R 0.942 PLAU_P11_F 0.941 PDE1B_E141_F 0.941 CCKAR_E79_F 0.940 p16_seq_47_S85_F 0.940 BCR_P346_F 0.939 CTLA4_P1128_F 0.938 PRSS8_E134_R 0.938 ATP10A_P147_F 0.938 CTSH_E157_R 0.938 BMP3_E147_F 0.937 PENK_E26_F 0.936 TSC2_E140_F 0.936 EPHA2_P203_F 0.936 KRT13_P341_R 0.936 CDKN1C_P6_R 0.935 EFNB3_P442_R 0.935 CASP10_E139_F 0.935 RIPK3_P24_F 0.934 S100A12_P1221_R 0.934 EVI2A_E420_F 0.933 CREBBP_P712_R 0.933 DLC1_P695_F 0.932 ZP3_P220_F 0.931 EPHB6_E342_F 0.931 SRC_P164_F 0.930 APP_P179_R 0.930 AXL_E61_F 0.930 HOXC6_P585_R 0.930 WNT5A_E43_F 0.929 TNFRSF10B_E198_R 0.929 CDH1_P45_F 0.929 IGF1_P933_F 0.928 AHR_P166_R 0.928 CCNA1_E7_F 0.928 CPA4_E20_F 0.927 WRN_E57_F 0.927 PSCA_P135_F 0.926 CDH17_E31_F 0.926 LRRK1_P39_F 0.925 GABRA5_P862_R 0.925 MAPK10_E26_F 0.924 SHB_P473_R 0.923 SEMA3F_E333_R 0.923 S100A2_E36_R 0.923 P2RX7_E323_R 0.922 IGFBP1_E48_R 0.922 NEU1_P745_F 0.922 NID1_P714_R 0.921 EPHB3_P569_R 0.921 UGT1A1_P315_R 0.921 ZIM2_E110_F 0.921 CASP10_P186_F 0.921 BCAM_E100_R 0.920 YES1_P600_F 0.920 IL12A_E287_R 0.918 NNAT_P544_R 0.918 COL1A1_P5_F 0.917 PITX2_P183_R 0.916 BMP4_P199_R 0.916 WNT10B_P823_R 0.915 SNCG_P53_F 0.915 PDGFA_P841_R 0.914 SOX17_P287_R 0.914 CDKN1A_E101_F 0.914 ABCA1_E120_R 0.914 ITK_P114_F 0.914 CD9_P504_F 0.913 PADI4_P1158_R 0.913 NPY_P295_F 0.913 DAPK1_E46_R 0.913 AIM2_P624_F 0.911 GPR116_E328_R 0.911 MYOD1_E156_F 0.910 SPI1_P929_F 0.910 GPX1_E46_R 0.910 SNCG_E119_F 0.909 HOXC6_P456_R 0.909 SOX1_P294_F 0.909 PITX2_E24_R 0.909 TYRO3_P501_F 0.909 HLA-DOA_P191_R 0.909 TFF2_P557_R 0.907 ESR1_P151_R 0.907 HLA-DPB1_E2_R 0.907 TESK2_P252_R 0.906 NOS2A_P288_R 0.905 KLK10_P268_R 0.905 ETV1_P235_F 0.905 TNFRSF1B_P167_F 0.905 SLIT2_P208_F 0.905 IFNGR2_P377_R 0.904 PLA2G2A_P528_F 0.904 FLT3_E326_R 0.904 LIF_P383_R 0.904 SIN3B_P607_F 0.904 MAF_E77_R 0.904 MCAM_P265_R 0.904 ALK_P28_F 0.904 ZNF264_P397_F 0.904 PDGFRB_P273_F 0.903 CSF1R_P73_F 0.903 PTCH2_E173_F 0.902 GLI2_P295_F 0.901 RARA_P1076_R 0.900

SUPPLEMENTAL TABLE 12 CpG loci which contribute most strongly to Random Forests classification of normal versus tumor bladder samples. GENE_CpG Percent Increase in MSE HPSE_P29_F 14.92 INSR_E97_F 14.39 MLH3_P25_F 14.34 TRAF4_P372_F 14.25 NPR2_P1093_F 14.16 MLF1_P97_F 14.12 KRAS_P651_F 14.11 VAMP8_E7_F 14.04 PPARD_P846_F 13.97 MCM2_P241_R 13.79 LAMB1_E144_R 13.74 COL6A1_P425_F 13.73 SERPINB5_P19_R 13.73 TK1_P62_R 13.72 EPHB4_E476_R 13.65 RARRES1_P57_R 13.64 HOXA9_P303_F 13.62 ABCG2_P178_R 13.55 TJP2_P518_F 13.51 IGSF4C_E65_F 13.43 MLH3_E72_F 13.38 COPG2_P298_F 13.17 DST_P262_R 13.04 MCM2_P260_F 12.98 IGF2R_P396_R 12.96 HPSE_P93_F 12.90 ABL2_P459_R 12.81 NTRK2_P395_R 12.73 ENC1_P484_R 12.56 CASP8_E474_F 12.51 MUC1_E18_R 11.00 IGF1R_P325_R 10.95 NOTCH3_P198_R 10.75 PTHR1_P258_F 10.60 PI3_P274_R 10.37 TRIM29_P261_F 10.32 ERCC6_P698_R 10.31 EMR3_P39_R 10.31 DHCR24_P406_R 10.29 KCNQ1_E349_R 10.28 CEACAM1_P44_R 10.22 ITGB4_E144_F 10.11 EPHA3_P106_R 10.00 CDKN1B_P1161_F 9.96 STK11_P295_R 9.94 NOS3_P38_F 9.79 EIF2AK2_E103_R 9.69 VAMP8_P114_F 9.58 PTPRH_E173_F 9.49 SFN_P248_F 9.47 CTNNA1_P382_R 9.45 SOX1_P1018_R 9.43 PCDH1_E22_F 9.35 CDH3_P87_R 9.27 NBL1_P24_F 9.18 CEACAM1_E57_R 9.15 TRIM29_E189_F 9.11 APOC1_P406_R 9.08 SFTPA1_E340_R 8.99 NBL1_E205_R 8.97 PTPN6_P282_R 8.91 APP_E8_F 8.83 ICAM1_P119_R 8.63 HLA-DOB_E432_R 8.62 FGFR2_P460_R 8.42 FER_E119_F 8.37 RASA1_E107_F 8.06 EMR3_E61_F 7.93 IL1B_P829_F 7.93 PTK6_E50_F 7.90 NID1_P677_F 7.89 ID1_P880_F 7.88 MMP7_E59_F 7.69 TFAP2C_P765_F 7.57 PTCH_E42_F 7.13 ACVR1C_P115_R 7.10 SHB_P691_R 7.09 CASP10_P186_F 7.07 GNMT_E126_F 7.03 TNFRSF10A_P91_F 6.76 HDAC1_P414_R 6.54 ETV1_P235_F 6.42 INHA_P1144_R 6.40 TRIM29_P135_F 6.35 S100A2_P1186_F 6.25 IGFBP1_P12_R 6.23 PENK_P447_R 6.15 TUBB3_P364_F 6.12 IFNGR1_P307_F 5.98 BAX_E281_R 5.90 MATK_P190_R 5.78 DDR1_P332_R 5.72 TJP2_P330_R 5.71 IL1RN_E42_F 5.69 SMARCA3_P109_R 5.66 WNT2B_P1195_F 5.60 PLXDC1_E71_F 5.47 DDB2_P407_F 5.42 CTSH_P238_F 5.27 AIM2_E208_F 5.24 INHA_P1189_F 5.15 TGFB2_P632_F 5.11 HS3ST2_E145_R 5.03 RYK_P493_F 5.02

SUPPLEMENTAL TABLE 13 Locus by locus analysis of CpGs with significantly differential methylation between normal bladder tissue and bladder tumor tissues. Regression GENE_CpG Coefficient* P-value Q-Value ABCG2_P178_R −0.90 0.000000 0.000000 ABL2_P459_R −1.30 0.000000 0.000000 ACVR1C_P115_R −1.37 0.000000 0.000000 CASP10_P186_F −1.74 0.000000 0.000000 CASP8_E474_F −2.13 0.000000 0.000000 CEACAM1_E57_R −1.76 0.000000 0.000000 COL6A1_P425_F −1.23 0.000000 0.000000 CTNNA1_P382_R −0.91 0.000000 0.000000 CTSH_P238_F −1.39 0.000000 0.000000 DHCR24_P406_R −1.51 0.000000 0.000000 DST_P262_R −0.79 0.000000 0.000000 EIF2AK2_E103_R −0.92 0.000000 0.000000 ENC1_P484_R −0.78 0.000000 0.000000 EPHB2_E297_F −0.95 0.000000 0.000000 EPHB4_E476_R −2.41 0.000000 0.000000 FER_E119_F −1.67 0.000000 0.000000 FGFR2_P460_R −1.72 0.000000 0.000000 GNMT_E126_F −0.97 0.000000 0.000000 HPSE_P29_F −1.94 0.000000 0.000000 HPSE_P93_F −1.02 0.000000 0.000000 ICA1_P61_F −0.84 0.000000 0.000000 ICAM1_P119_R −1.42 0.000000 0.000000 IGF1R_P325_R −0.78 0.000000 0.000000 IGF2R_P396_R −1.60 0.000000 0.000000 INHA_P1144_R −1.07 0.000000 0.000000 INSR_E97_F −0.92 0.000000 0.000000 ITGB4_E144_F −1.07 0.000000 0.000000 KCNQ1_E349_R −1.01 0.000000 0.000000 LAMB1_E144_R −1.44 0.000000 0.000000 MCM2_P241_R −1.09 0.000000 0.000000 MCM2_P260_F −1.42 0.000000 0.000000 MLF1_P97_F −2.24 0.000000 0.000000 MLH3_P25_F −1.81 0.000000 0.000000 MMP7_E59_F −1.83 0.000000 0.000000 NPR2_P1093_F 1.50 0.000000 0.000000 PCDH1_E22_F −0.76 0.000000 0.000000 PPARD_P846_F −2.03 0.000000 0.000000 PTCH_E42_F −0.81 0.000000 0.000000 RASA1_E107_F −0.88 0.000000 0.000000 TFAP2C_P765_F −1.16 0.000000 0.000000 TGFB2_P632_F −0.80 0.000000 0.000000 TJP2_P518_F 3.38 0.000000 0.000000 TK1_P62_R −1.34 0.000000 0.000000 TNFRSF10A_P91_F −1.59 0.000000 0.000000 TRAF4_P372_F −1.64 0.000000 0.000000 VAMP8_P114_F −2.24 0.000000 0.000000 WNT2B_P1195_F −1.00 0.000000 0.000000 ID1_P880_F −1.29 0.000000 0.000000 IL1B_P829_F 1.21 0.000000 0.000000 ITGA2_E120_F −1.13 0.000000 0.000000 AHR_P166_R −1.16 0.000000 0.000000 PDGFA_P841_R −0.79 0.000000 0.000000 STK11_P295_R −1.55 0.000000 0.000000 PTK6_E50_F −1.97 0.000000 0.000000 SFN_P248_F −1.43 0.000000 0.000000 PLXDC1_E71_F −1.01 0.000000 0.000000 FGFR2_P266_R −1.01 0.000000 0.000000 HDAC1_P414_R −2.14 0.000000 0.000000 IGSF4C_E65_F −1.94 0.000000 0.000000 DSP_P36_F −1.26 0.000000 0.000000 MGMT_P272_R −1.12 0.000000 0.000000 ERCC6_P698_R −1.58 0.000000 0.000000 TNFRSF10A_P171_F −1.39 0.000000 0.000000 MAP3K1_P7_F −1.16 0.000000 0.000000 MUC1_E18_R −2.14 0.000000 0.000000 CD9_E14_R −0.78 0.000000 0.000000 FER_P581_F 1.82 0.000000 0.000000 CEACAM1_P44_R −1.83 0.000000 0.000000 KRAS_P651_F −0.73 0.000000 0.000000 MYCN_E77_R −0.77 0.000000 0.000000 BCAM_P205_F −1.03 0.000000 0.000000 APP_E8_F −0.87 0.000000 0.000000 EPS8_E231_F −0.92 0.000000 0.000000 SHB_P691_R −1.41 0.000000 0.000000 CPA4_P961_R 0.87 0.000000 0.000000 INHA_P1189_F −0.94 0.000000 0.000000 NBL1_P24_F −2.22 0.000000 0.000000 TYRO3_P501_F −1.09 0.000000 0.000000 CAPG_E228_F −1.71 0.000000 0.000000 PTPRH_E173_F −1.76 0.000000 0.000000 TNFSF10_E53_F −1.30 0.000000 0.000000 JAG1_P66_F −0.82 0.000000 0.000000 DDR1_E23_R −1.12 0.000000 0.000000 PHLDA2_P622_F −1.38 0.000000 0.000000 CPNE1_P138_F −1.16 0.000000 0.000000 NOTCH3_P198_R −1.70 0.000000 0.000000 PCGF4_P760_R −1.21 0.000000 0.000000 WRN_E57_F −0.97 0.000000 0.000000 RIPK3_P124_F −1.82 0.000000 0.000000 VAMP8_E7_F −1.51 0.000000 0.000000 SHB_P473_R −0.68 0.000000 0.000000 BCL3_E71_F −1.07 0.000000 0.000000 RARRES1_P57_R −1.62 0.000000 0.000000 GAS1_P754_R −0.58 0.000000 0.000000 PRKAR1A_P337_R −0.86 0.000000 0.000000 SYK_E372_F −0.73 0.000000 0.000000 COPG2_P298_F 1.43 0.000000 0.000000 WNT2B_P1185_R −1.12 0.000000 0.000000 PTHR1_P258_F −1.79 0.000000 0.000000 EMR3_E61_F −1.79 0.000000 0.000000 IGFBP1_P12_R −2.16 0.000000 0.000000 CCND1_P343_R −1.26 0.000000 0.000000 CASP6_P230_R −1.22 0.000000 0.000000 PAX6_E129_F −1.06 0.000000 0.000000 MATK_P190_R −1.82 0.000000 0.000000 PHLDA2_E159_R −0.70 0.000000 0.000000 CDH3_E100_R −0.80 0.000000 0.000000 APP_P179_R −0.83 0.000000 0.000001 EPHA3_P106_R 2.65 0.000000 0.000001 PKD2_P287_R −0.77 0.000000 0.000001 SPDEF_E116_R −1.64 0.000000 0.000001 EFNB3_P442_R −0.80 0.000000 0.000001 RIPK4_E166_F −1.04 0.000000 0.000001 BAX_E281_R −1.40 0.000000 0.000001 AXL_E61_F −1.08 0.000000 0.000001 HBII-13_P991_R 0.77 0.000000 0.000001 RHOH_P121_F 1.14 0.000000 0.000001 PTGS1_E80_F −0.86 0.000000 0.000001 FGFR3_E297_R −0.49 0.000000 0.000002 CDH1_P45_F −1.09 0.000000 0.000002 MMP14_P208_R −1.33 0.000000 0.000002 GSTM1_P363_F 1.01 0.000001 0.000003 CDKN1A_E101_F −0.63 0.000001 0.000003 MMP9_P237_R −0.77 0.000001 0.000003 MYCN_P464_R −0.49 0.000001 0.000003 SEMA3F_E333_R −1.14 0.000001 0.000004 SEMA3F_P692_R −0.70 0.000001 0.000004 DDB2_P407_F −1.01 0.000001 0.000004 TJP2_P330_R 2.96 0.000001 0.000005 S100A2_P1186_F −2.47 0.000001 0.000005 PTPN6_P282_R −2.32 0.000001 0.000006 IL8_P83_F −2.01 0.000001 0.000006 DST_E31_F −0.75 0.000001 0.000006 NOS3_P38_F −2.57 0.000002 0.000007 DDR1_P332_R −1.89 0.000002 0.000007 EMR3_P39_R −1.82 0.000002 0.000007 MLF1_E243_F 2.13 0.000002 0.000007 TUBB3_E91_F −1.56 0.000002 0.000007 JAG2_E54_F −0.54 0.000002 0.000008 EDN1_P39_R −0.36 0.000002 0.000008 KLK10_P268_R −0.88 0.000002 0.000008 SPDEF_P6_R −1.45 0.000002 0.000009 ACVR1B_E497_R −0.75 0.000002 0.000009 HDAC5_E298_F −0.83 0.000002 0.000009 COL4A3_P545_F −0.61 0.000003 0.000013 TIAM1_P117_F −0.95 0.000003 0.000013 BMPR1A_P956_F −0.73 0.000003 0.000013 BMPR2_E435_F 0.76 0.000003 0.000014 INSR_P1063_R −1.28 0.000004 0.000015 GSTM1_P266_F 1.56 0.000004 0.000015 TRIM29_P261_F −3.08 0.000004 0.000015 MYLK_E132_R −1.53 0.000004 0.000017 IL1RN_E42_F −2.32 0.000004 0.000017 BCAM_E100_R −0.47 0.000005 0.000018 B3GALT5_P330_F 0.55 0.000006 0.000021 EPHA2_P340_R −1.23 0.000006 0.000021 TYK2_P494_F −1.42 0.000006 0.000021 PDGFB_E25_R −0.89 0.000006 0.000023 IPF1_P750_F 2.03 0.000007 0.000025 HBEGF_P32_R −0.66 0.000007 0.000025 HLA-DPA1_P205_R −1.38 0.000007 0.000026 WNT5A_E43_F −0.63 0.000008 0.000028 ER_seq_a1_S60_F −1.04 0.000009 0.000031 IL12A_E287_R −0.53 0.000010 0.000034 AIM2_E208_F −1.91 0.000010 0.000035 CRK_P721_F −1.09 0.000010 0.000036 CDH3_P87_R 1.14 0.000010 0.000037 FN1_P229_R 0.93 0.000011 0.000037 TRIM29_E189_F −2.23 0.000013 0.000044 TFDP1_P543_R 0.74 0.000013 0.000045 CCR5_P630_R −1.21 0.000013 0.000046 ITGB1_P451_F −0.93 0.000016 0.000053 MTA1_P478_F −0.78 0.000017 0.000056 NPR2_P618_F 2.41 0.000017 0.000056 THY1_P20_R −1.23 0.000018 0.000058 VAMP8_P241_F −1.48 0.000018 0.000060 SMARCA4_P362_R −0.47 0.000019 0.000064 GNMT_P197_F −0.71 0.000020 0.000065 EPHB2_P165_R −0.96 0.000020 0.000066 CDKN2B_seq_50_S294_F 2.21 0.000021 0.000067 TNFRSF10B_E198_R −0.67 0.000021 0.000067 ITGB4_P517_F −0.82 0.000021 0.000067 MMP10_E136_R −1.52 0.000021 0.000068 ACTG2_P346_F 1.21 0.000022 0.000068 CSF3_P309_R −1.81 0.000024 0.000077 EGR4_E70_F −0.88 0.000028 0.000087 EPHB6_E342_F −1.06 0.000029 0.000089 IL8_E118_R −1.02 0.000029 0.000089 ACVR2B_E27_R −0.63 0.000031 0.000094 PYCARD_P150_F 1.20 0.000032 0.000097 AREG_E25_F −0.45 0.000032 0.000099 IGFBP3_E65_R 1.07 0.000039 0.000119 IL18BP_E285_F 0.65 0.000041 0.000124 FANCF_P13_F −0.57 0.000042 0.000128 TJP1_P326_R −0.80 0.000044 0.000133 TFF2_P178_F −2.25 0.000047 0.000139 IFNG_E293_F −1.65 0.000047 0.000140 SRC_E100_R −1.98 0.000050 0.000146 EPHA1_P119_R −0.82 0.000050 0.000148 NCL_P840_R −0.84 0.000053 0.000154 NBL1_E205_R −2.06 0.000053 0.000155 EPM2A_P64_R −0.55 0.000054 0.000155 CTTN_E29_R −0.84 0.000054 0.000155 IFNGR1_P307_F 0.81 0.000058 0.000164 VAV1_E9_F −1.90 0.000058 0.000164 BMP3_P56_R −0.45 0.000061 0.000171 PTPN6_E171_R −1.50 0.000061 0.000171 EGF_E339_F 1.30 0.000070 0.000196 SKI_E465_R −0.41 0.000071 0.000196 CLDN4_P1120_R −1.87 0.000071 0.000196 RARB_P60_F −1.17 0.000083 0.000228 IGF2AS_P203_F 1.90 0.000086 0.000237 PSIP1_P163_R −0.88 0.000086 0.000237 APOC1_P406_R −1.15 0.000087 0.000237 GAS1_E22_F −0.62 0.000091 0.000247 CXCL9_E268_R −2.11 0.000094 0.000254 MCC_P196_R 0.69 0.000097 0.000260 MBD2_P233_F −1.12 0.000101 0.000270 HLA-DOB_E432_R −1.49 0.000101 0.000270 TAL1_P594_F 2.69 0.000102 0.000271 PENK_P447_R 2.83 0.000110 0.000289 CYP1B1_E83_R 1.93 0.000111 0.000291 DAPK1_P345_R −0.86 0.000112 0.000293 EVI2A_E420_F 0.90 0.000115 0.000300 PSCA_E359_F −1.42 0.000120 0.000311 RYK_P493_F 2.41 0.000121 0.000314 ABCA1_E120_R −0.60 0.000132 0.000339 FRK_P36_F −1.61 0.000133 0.000342 NTRK2_P395_R 2.87 0.000146 0.000370 CTSH_E157_R 0.80 0.000146 0.000370 PTK7_E317_F −1.33 0.000155 0.000391 p16_seq_47_S85_F −1.06 0.000161 0.000405 MME_P388_F 2.63 0.000165 0.000413 FZD9_P15_R −0.99 0.000176 0.000439 THBS2_P605_R −1.58 0.000177 0.000440 EXT1_E197_F −0.71 0.000193 0.000477 IL1RN_P93_R −1.45 0.000197 0.000486 SNCG_P98_R −1.13 0.000205 0.000503 FRK_P258_F −1.68 0.000206 0.000503 KIAA1804_P689_R −0.92 0.000212 0.000517 TRIM29_P135_F −2.16 0.000216 0.000522 HIC-1_seq_48_S103_R 1.58 0.000222 0.000537 CDKN1C_P6_R −0.71 0.000240 0.000576 CPA4_E20_F −1.23 0.000268 0.000638 IGFBP1_E48_R −1.49 0.000268 0.000638 CASP10_E139_F −1.25 0.000275 0.000652 PDE1B_E141_F −0.73 0.000293 0.000693 LIG3_P622_R −1.38 0.000299 0.000704 SLC14A1_E295_F −2.08 0.000312 0.000732 JAK3_P1075_R −1.56 0.000314 0.000733 PLAU_P11_F −0.95 0.000326 0.000759 MYBL2_P354_F −1.30 0.000331 0.000767 FLI20712_P984_R −1.47 0.000338 0.000778 DLC1_P695_F −1.26 0.000339 0.000778 CTSD_P726_F −1.08 0.000360 0.000825 TFAP2C_E260_F 2.63 0.000375 0.000855 CARD15_P302_R −1.21 0.000378 0.000859 EPHA2_P203_F −1.23 0.000386 0.000873 SNCG_P53_F −1.41 0.000397 0.000894 ERBB3_E331_F −0.78 0.000403 0.000904 BMP3_E147_F −0.78 0.000413 0.000924 SERPINB5_P19_R −3.04 0.000418 0.000931 HOXA9_P1141_R 1.54 0.000426 0.000946 BCR_P422_F −1.46 0.000447 0.000988 DAB2IP_E18_R −0.58 0.000473 0.001041 BCR_P346_F −1.32 0.000476 0.001044 DSP_P440_R −0.87 0.000495 0.001082 TSC2_E140_F −1.08 0.000503 0.001096 SPP1_P647_F −1.71 0.000519 0.001127 TFF1_P180_R −1.47 0.000525 0.001135 TUSC3_P85_R −0.94 0.000536 0.001155 SFN_E118_F −2.05 0.000564 0.001211 TRIP6_P1090_F −1.78 0.000569 0.001217 RIPK4_P172_F −0.63 0.000610 0.001299 GPX1_E46_R −0.60 0.000614 0.001304 FGFR3_P1152_R −1.43 0.000630 0.001332 NOS2A_E117_R −2.07 0.000636 0.001340 IGF1_P933_F −1.12 0.000677 0.001421 CTLA4_P1128_F −1.08 0.000690 0.001443 RIPK3_P24_F −1.36 0.000718 0.001495 EPHB3_P569_R −0.69 0.000720 0.001495 ERCC1_P440_R −0.60 0.000763 0.001581 DLK1_E227_R 2.80 0.000795 0.001639 MAF_E77_R −0.67 0.000811 0.001667 BMP2_P1201_F −0.94 0.000829 0.001698 P2RX7_P597_F −2.74 0.000855 0.001746 P2RX7_E323_R −0.71 0.000873 0.001776 RBP1_P426_R 1.92 0.000878 0.001779 NID1_P677_F −2.46 0.000902 0.001822 MYB_P673_R −0.65 0.000909 0.001826 LRRK1_P39_F −0.56 0.000910 0.001826 EVI1_E47_R −0.74 0.000923 0.001845 PADI4_P1158_R −1.15 0.000944 0.001881 MAPK10_E26_F −1.52 0.000955 0.001897 TMPRSS4_E83_F −2.48 0.001014 0.002006 TIMP2_E394_R −0.35 0.001061 0.002087 EPHA1_E46_R −0.72 0.001062 0.002087 HDAC7A_P344_F 0.45 0.001069 0.002094 S100A12_P1221_R 0.58 0.001093 0.002135 PI3_E107_F −2.33 0.001124 0.002187 LAT_E46_F 0.87 0.001137 0.002204 RIPK1_P744_R 0.79 0.001154 0.002231 DAPK1_E46_R −0.87 0.001166 0.002246 CDH17_P376_F −2.39 0.001187 0.002279 ERBB4_P255_F −0.44 0.001275 0.002434 EGF_P413_F −1.74 0.001276 0.002434 ACVR2B_P676_F −0.60 0.001323 0.002516 S100A2_E36_R −0.79 0.001482 0.002809 NOS2A_P288_R −1.17 0.001503 0.002840 WNT5A_P655_F 2.57 0.001508 0.002840 MLH3_E72_F 1.90 0.001530 0.002867 MST1R_E42_R −1.70 0.001532 0.002867 BMP4_P199_R −1.27 0.001546 0.002883 PRSS8_E134_R −1.67 0.001635 0.003040 MCAM_P265_R −0.68 0.001653 0.003064 PDGFRB_P273_F −1.02 0.001720 0.003178 APBA2_P305_R −1.74 0.001741 0.003206 PI3_P274_R −2.12 0.001774 0.003256 YES1_P600_F 1.50 0.001847 0.003381 PSCA_P135_F −1.26 0.001854 0.003382 PTPRH_P255_F −2.10 0.001878 0.003415 PPARG_E178_R −0.32 0.001977 0.003576 ABCA1_P45_F −0.62 0.001979 0.003576 ZIM2_E110_F 0.74 0.002078 0.003744 CAV2_E33_R −0.44 0.002103 0.003778 EPO_P162_R −1.15 0.002134 0.003821 CSF1R_P73_F −1.03 0.002147 0.003833 ZP3_P220_F −1.39 0.002237 0.003981 SNCG_E119_F −1.16 0.002290 0.004063 IHH_P529_F −0.49 0.002300 0.004070 IFNGR2_P377_R 1.32 0.002326 0.004101 MMP9_P189_F −1.03 0.002334 0.004101 CDH1_P52_R −0.68 0.002339 0.004101 KLF5_E190_R −0.66 0.002414 0.004219 GATA6_P21_R −1.00 0.002540 0.004426 SEMA3C_E49_R −0.68 0.002578 0.004479 PENK_E26_F 1.59 0.002614 0.004528 COL1A1_P5_F 1.18 0.002716 0.004691 PTCH2_E173_F −0.84 0.002895 0.004986 CREBBP_P712_R −1.64 0.002981 0.005119 SRC_P164_F −1.74 0.003173 0.005432 HOXC6_P585_R 1.50 0.003214 0.005486 LIF_P383_R −0.95 0.003225 0.005489 FOLR1_E368_R 0.48 0.003252 0.005509 IRF5_E101_F 0.80 0.003255 0.005509 HLA-DOA_P191_R −1.02 0.003311 0.005587 ATP10A_P147_F 1.87 0.003442 0.005790 COL18A1_P494_R −1.07 0.003487 0.005850 SOX1_P1018_R 3.40 0.003538 0.005918 SPI1_P929_F −1.00 0.003630 0.006054 TWIST1_P355_R 2.19 0.003648 0.006067 MXI1_P75_R −0.72 0.003694 0.006113 PLAUR_E123_F −0.32 0.003697 0.006113 CCKAR_E79_F −1.96 0.003736 0.006161 ETS1_P559_R −0.36 0.003785 0.006224 NNAT_P544_R 0.81 0.003837 0.006293 SMAD2_P848_R −0.70 0.004038 0.006603 SOX17_P287_R 1.42 0.004059 0.006619 KRT13_P341_R −2.14 0.004079 0.006634 HS3ST2_E145_R 2.68 0.004175 0.006771 GABRA5_P1016_F −2.11 0.004192 0.006779 CDKN1B_P1161_F 2.85 0.004289 0.006888 TNFRSF1B_P167_F −0.96 0.004294 0.006888 ZNF264_P397_F 1.00 0.004294 0.006888 UGT1A1_P315_R −1.63 0.004343 0.006946 TK1_E47_F 0.54 0.004497 0.007174 ETV6_E430_F 0.80 0.004590 0.007301 WNT10B_P823_R −1.23 0.004614 0.007320 CASP6_P201_F −0.72 0.004915 0.007756 HLA-DPB1_E2_R −1.17 0.004920 0.007756 PLA2G2A_P528_F −1.12 0.004929 0.007756 HOXA9_E252_R 3.16 0.004956 0.007778 GNG7_E310_R 0.58 0.004986 0.007803 PITX2_P183_R 1.55 0.005098 0.007958 IRF5_P123_F −0.38 0.005189 0.008078 PLAUR_P82_F −0.53 0.005291 0.008214 THBS1_E207_R 0.62 0.005335 0.008262 EDN1_E50_R 0.85 0.005405 0.008347 JAK2_P772_R −0.79 0.005564 0.008570 CDH17_E31_F −2.09 0.005812 0.008929 ITK_P114_F −1.58 0.005867 0.008983 LY6G6E_P45_R −1.30 0.005878 0.008983 TGFA_P642_R −0.54 0.006026 0.009185 RARA_P1076_R −1.26 0.006143 0.009339 PKD2_P336_R −0.49 0.006180 0.009372 SMAD2_P708_R −0.30 0.006199 0.009375 KLF5_P13_F −0.62 0.006385 0.009632 GLI2_P295_F −1.20 0.006417 0.009636 GABRA5_P862_R −1.71 0.006421 0.009636 NID1_P714_R −1.95 0.006747 0.010093 SPP1_E140_R −0.95 0.006760 0.010093 AATK_E63_R −2.65 0.006785 0.010105 MGMT_P281_F −0.40 0.007025 0.010435 GPR116_E328_R −1.77 0.007152 0.010587 EPHA5_P66_F 1.00 0.007166 0.010587 CTNNA1_P185_R −0.42 0.007181 0.010587 TRPM5_P721_F −1.11 0.007361 0.010824 CDK10_P199_R −0.73 0.007450 0.010928 ICA1_P72_R −0.46 0.007610 0.011113 ESR1_P151_R 1.67 0.007648 0.011113 FGFR4_P610_F −1.22 0.007656 0.011113 CD34_P339_R 0.74 0.007666 0.011113 CD9_P504_F 1.80 0.007672 0.011113 IL12B_P1453_F −1.07 0.007831 0.011316 ZAP70_P220_R −0.92 0.007872 0.011347 AIM2_P624_F −1.60 0.008154 0.011724 DCC_E53_R 1.21 0.008226 0.011800 LIG4_P194_F −0.41 0.008322 0.011908 TFF2_P557_R −1.79 0.008410 0.012000 LCN2_P86_R −1.38 0.008428 0.012000 TESK2_P252_R 1.70 0.008595 0.012194 MLLT6_P957_F −0.60 0.008606 0.012194 SFTPA1_E340_R −3.13 0.008634 0.012205 IHH_P246_R −0.54 0.008983 0.012668 LCN2_P141_R −1.41 0.009336 0.013133 TNFRSF10B_P108_R −0.57 0.009494 0.013324 FES_E34_R −0.96 0.009543 0.013359 CD34_P780_R −0.91 0.009868 0.013781 SLC22A18_P472_R 0.61 0.010237 0.014263 HOXA9_P303_F 3.60 0.010269 0.014273 DNAJC15_P65_F 0.57 0.010630 0.014740 JAG2_P264_F −0.40 0.010668 0.014757 CASP10_P334_F −0.74 0.011116 0.015341 ELL_P693_F −1.04 0.011261 0.015505 PITX2_E24_R 1.71 0.011459 0.015704 DSG1_P159_R −1.16 0.011460 0.015704 DUSP4_P925_R 1.12 0.011505 0.015729 HOXC6_P456_R 1.65 0.011556 0.015762 PTGS2_P524_R 1.12 0.011628 0.015823 PDE1B_P263_R 1.68 0.012706 0.017250 DDB2_P613_R 1.02 0.013101 0.017745 PTHLH_P15_R −1.16 0.013273 0.017936 NEU1_P745_F 2.24 0.013342 0.017988 SOX17_P303_F 1.67 0.013592 0.018283 FGF1_E5_F −1.15 0.013716 0.018407 GLI3_E148_R 0.49 0.014037 0.018795 PLAGL1_P334_F 0.61 0.014308 0.019048 NAT2_P11_F 0.75 0.014320 0.019048 ALK_P28_F −0.96 0.014326 0.019048 SIN3B_P607_F 0.69 0.014356 0.019048 NPY_P295_F 2.01 0.014576 0.019295 IL2_P607_R −1.22 0.014664 0.019369 TERT_P360_R 1.79 0.014931 0.019676 ALPL_P433_F 0.95 0.015004 0.019727 CSF2_E248_R −1.67 0.015178 0.019912 CCNA1_E7_F 2.64 0.015347 0.020088 SRC_P297_F −1.52 0.015743 0.020542 RARRES1_P426_R −0.92 0.015764 0.020542 HOXA11_P698_F 1.66 0.015881 0.020649 TCF7L2_P193_R 0.94 0.016138 0.020936 OGG1_E400_F −1.01 0.016210 0.020974 KRT5_P308_F −1.23 0.016239 0.020974 CHFR_P501_F −0.62 0.016392 0.021124 NQO1_E74_R 1.40 0.016475 0.021184 WNT8B_P216_R 0.39 0.016764 0.021510 HSD17B12_E145_R −0.39 0.016998 0.021761 LIF_E208_F −0.26 0.017342 0.022154 TMEFF2_P210_R 1.43 0.017680 0.022536 OSM_P34_F −1.20 0.017742 0.022566 TMEFF2_P152_R 1.66 0.018033 0.022886 SOX1_P294_F 2.16 0.018308 0.023185 ESR2_P162_F −0.63 0.018932 0.023923 GSTM2_P453_R 0.88 0.019014 0.023975 JAK3_P156_R 1.32 0.019289 0.024269 MYOD1_E156_F 2.46 0.019334 0.024274 FLT3_E326_R 2.17 0.019570 0.024517 CD34_E20_R −0.52 0.019759 0.024701 ABCC5_P444_F −0.46 0.019937 0.024870 TRPM5_P979_F −1.62 0.020010 0.024907 BSG_P211_R −0.76 0.020209 0.025102 TAL1_P817_F 0.78 0.020559 0.025483 FGFR1_E317_F −0.37 0.021156 0.026166 H19_P1411_R −1.21 0.021369 0.026374 NOTCH3_E403_F 1.87 0.021510 0.026492 APBA2_P227_F −1.92 0.021681 0.026617 DCC_P471_R 1.86 0.021703 0.026617 GLI2_E90_F −1.58 0.021883 0.026782 CDH11_P354_R 1.12 0.022092 0.026981 HDAC11_P556_F −0.49 0.022411 0.027314 DES_P1006_R −0.79 0.023085 0.028061 PTHLH_E251_F −0.84 0.023120 0.028061 BDNF_P259_R 1.25 0.023219 0.028123 SLIT2_P208_F 2.19 0.023277 0.028134 VAV2_P1182_F 0.36 0.023363 0.028180 HTR1B_P107_F −1.13 0.023509 0.028267 CSF2_P605_F −1.46 0.023532 0.028267 NOTCH2_P312_R −0.35 0.023764 0.028451 ACVR1C_P363_F −0.91 0.023809 0.028451 ESR1_E298_R −0.72 0.023864 0.028451 FGF1_P357_R −0.99 0.023880 0.028451 ITPR2_P804_F 0.71 0.023951 0.028477 SEMA3A_P658_R −0.66 0.024125 0.028626 EPHA8_P456_R −1.05 0.024815 0.029385 HCK_P858_F 1.22 0.024869 0.029390 DLL1_P832_F 1.33 0.024954 0.029430 BMP6_P163_F −0.75 0.025012 0.029439 EPS8_P437_F −0.48 0.025183 0.029580 CCNA1_P216_F 2.03 0.025372 0.029743 ERCC1_P354_F −0.40 0.025473 0.029802 LEFTY2_P561_F 0.65 0.025606 0.029897 PWCR1_P357_F −0.60 0.026077 0.030387 MST1R_P87_R −1.05 0.026820 0.031190 TGFBR3_E188_R −0.47 0.026917 0.031241 CSF1R_E26_F −1.34 0.027384 0.031720 CSK_P740_R −0.64 0.028023 0.032392 FOSL2_E384_R −0.95 0.028076 0.032392 MEG3_E91_F 0.68 0.028144 0.032407 GFAP_P1214_F 0.63 0.028629 0.032866 PADI4_E24_F −1.24 0.028656 0.032866 SERPINA5_P156_F −0.76 0.028730 0.032887 HLA-DRA_P77_R −0.90 0.028803 0.032905 NGFB_E353_F −0.72 0.028982 0.033045 UBA52_P293_R 1.86 0.029060 0.033071 ABCG2_P310_R −0.36 0.029338 0.033321 ETV1_P235_F 2.29 0.029498 0.033438 WNT10B_P993_F −0.89 0.029716 0.033620 SPARC_P195_F 1.01 0.030936 0.034933 SEMA3C_P642_F −1.09 0.031939 0.035995 TFRC_P414_R 1.19 0.032087 0.036093 DIO3_E230_R 0.77 0.032778 0.036737 AOC3_P890_R −0.80 0.032832 0.036737 TMEFF1_P234_F 0.85 0.032848 0.036737 MMP19_E274_R −0.96 0.033497 0.037391 EPHB1_P503_F 1.08 0.033597 0.037403 KIAA0125_E29_F −1.06 0.033636 0.037403 PTPNS1_P301_R −0.44 0.033720 0.037425 CYP2E1_P416_F −2.11 0.033809 0.037452 DNAJC15_E26_R 1.12 0.033947 0.037535 TWIST1_P44_R 2.12 0.035115 0.038752 ROR1_P6_F 0.76 0.035599 0.039212 ERBB4_P541_F −0.42 0.035854 0.039297 GRB7_P160_R −0.69 0.035953 0.039297 DNMT1_P100_R 0.86 0.035965 0.039297 ST6GAL1_P528_F 2.02 0.035969 0.039297 FVT1_P225_F −0.55 0.036013 0.039297 CCL3_P543_R −0.95 0.036372 0.039615 CSPG2_P82_R 1.40 0.037499 0.040767 KRT5_E196_R −2.00 0.038665 0.041956 SFTPA1_P421_F −0.92 0.038848 0.042076 CHFR_P635_R −0.23 0.039059 0.042185 TCF4_P317_F 1.49 0.039093 0.042185 EYA4_E277_F 1.40 0.039614 0.042668 LAMC1_P808_F 1.07 0.039977 0.042981 NEFL_P209_R 1.51 0.040064 0.042994 EDNRB_P709_R −1.99 0.040169 0.043028 SH3BP2_E18_F −0.70 0.040523 0.043327 SYK_P584_F −0.66 0.040905 0.043657 GP1BB_P278_R −1.03 0.041121 0.043806 MC2R_E455_F −1.90 0.041831 0.044482 B3GALT5_E246_R −0.92 0.042345 0.044947 SPI1_E205_F 0.40 0.042446 0.044972 ERN1_P809_R −1.03 0.043701 0.046218 ZIM3_P718_R −1.41 0.044043 0.046495 HDAC9_P137_R 1.11 0.044490 0.046882 NOTCH4_E4_F −0.93 0.045992 0.048378 HOXA5_P1324_F 0.91 0.046268 0.048580 EPHB1_E202_R −0.66 0.046952 0.049190 TEK_E75_F −0.90 0.047017 0.049190 RARRES1_E235_F −0.77 0.047130 0.049220 DUSP4_E61_F −0.39 0.047370 0.049382 MCM6_E136_F −0.44 0.047758 0.049698 DSG1_E292_F −0.56 0.047869 0.049725 IAPP_E280_F −1.32 0.048108 0.049885 *Positive coefficient indicates higher methylation in bladder tumors relative to normal bladder tissues

SUPPLEMENTAL TABLE 14 Comparing methylation of CpG loci between normal bladder tissue and bladder tumors, those loci with a q-value < 1 × 10⁻⁶ (n = 107), an AUC of ≧0.98, and a percent change to the RF MSE ≧5% were compared and 65 loci were identified to overlap between these 3 approaches. GENE_CpG ABCG2_P178_R MLH3_P25_F ABL2_P459_R MMP7_E59_F ACVR1C_P115_R MUC1_E18_R APP_E8_F NBL1_P24_F CASP8_E474_F NOTCH3_P198_R CEACAM1_E57_R NPR2_P1093_F CEACAM1_P44_R PCDH1_E22_F COL6A1_P425_F PLXDC1_E71_F COPG2_P298_F PPARD_P846_F CTNNA1_P382_R PTHR1_P258_F DHCR24_P406_R PTK6_E50_F DST_P262_R PTPRH_E173_F EIF2AK2_E103_R RARRES1_P57_R EMR3_E61_F RASA1_E107_F ENC1_P484_R SFN_P248_F EPHB4_E476_R SHB_P691_R ERCC6_P698_R STK11_P295_R FER_E119_F TFAP2C_P765_F FGFR2_P460_R TGFB2_P632_F GNMT_E126_F TJP2_P518_F HDAC1_P414_R TK1_P62_R HPSE_P29_F TNFRSF10A_P91_F HPSE_P93_F TRAF4_P372_F ICAM1_P119_R VAMP8_E7_F ID1_P880_F VAMP8_P114_F IGF1R_P325_R IGF2R_P396_R IGFBP1_P12_R IGSF4C_E65_F IL1B_P829_F INHA_P1144_R INSR_E97_F ITGB4_E144_F KCNQ1_E349_R KRAS_P651_F LAMB1_E144_R MATK_P190_R MCM2_P241_R MCM2_P260_F MLF1_P97_F

SUPPLEMENTAL TABLE 15 Locus by locus analysis of CpG loci with differential methylation in invasive bladder tumors relative to non-invasive tumors from tumor series 1 and tumor series 2. Series 1 Series 2 Regression Regression GENE_CpG coefficient* P-value Q-value GENE_CpG coefficient* P-value Q-value SLC14A1_E295_F 1.34 0 0 GP1BB_P278_R 1.39 0 0 RARA_P1076_R 1.42 0 1.00E−06 SLIT2_E111_R 1.14 0 0 EGF_P413_F 1.09 0 1.00E−06 FGF3_E198_R 1.55 0 0 KRT13_P341_R 1.21 0 1.00E−06 STAT5A_P704_R 1.15 0 0 CSF1R_P73_F 0.92 0 1.00E−06 CDH11_E102_R 1.57 0 0 FGFR4_P610_F 0.89 0 2.00E−06 KRT13_P341_R 1.02 0 0 UGT1A1_P315_R 1.04 0 3.00E−06 FGF1_P357_R 0.92 0 0 STAT5A_P704_R 1.22 0 4.00E−06 SLIT2_P208_F 1.38 0 0 MAP3K1_P7_F 0.52 0 5.00E−06 EYA4_E277_F 1.30 0 0 IRF5_P123_F 0.35 0 6.00E−06 RASSF1_E116_F 1.63 0 0 RIPK1_P868_F 0.83 0 6.00E−06 HOXB2_P488_R 1.22 0 0 CSF1R_E26_F 1.01 0 7.00E−06 CSF3_P309_R 0.92 0 0 TEK_E75_F 1.09 0 7.00E−06 CDH13_E102_F 1.29 0 0 FGF1_P357_R 1.00 0 7.00E−06 HPN_P374_R 1.03 0 0 TRPM5_P979_F 1.20 0 7.00E−06 TNFRSF10C_P7_F 1.04 0 0 SNCG_E119_F 1.05 0 1.00E−05 TERT_P360_R 0.92 0 0 AATK_E63_R 1.25 1.00E−06 1.80E−05 HS3ST2_P171_F 1.25 0 0 SLC14A1_P369_R 1.15 1.00E−06 1.90E−05 SOX1_P294_F 1.20 0 0 FGF1_E5_F 0.91 1.00E−06 2.40E−05 TPEF_seq_44_S36_F 1.13 0 0 CSF2_P605_F 1.07 1.00E−06 2.50E−05 NTSR1_P318_F 1.21 0 0 HPN_P374_R 1.10 1.00E−06 3.00E−05 DES_E228_R 1.02 0 0 CSF3_P309_R 1.09 1.00E−06 3.40E−05 NOTCH4_E4_F 1.06 0 0 TMPRSS4_E83_F 0.99 2.00E−06 5.20E−05 FGF3_P171_R 1.29 0 0 AIM2_E208_F 0.60 3.00E−06 6.60E−05 GDF10_P95_R 1.19 0 0 AATK_P519_R 1.07 3.00E−06 6.80E−05 VIM_P343_R 1.26 0 0 CDH17_P376_F 0.95 4.00E−06 7.30E−05 MST1R_E42_R 1.01 0 0 MMP7_E59_F 0.62 4.00E−06 8.00E−05 GAS7_P622_R 1.17 0 0 THBS2_P605_R 0.87 4.00E−06 8.00E−05 VAV1_E9_F 1.08 0 0 KLK10_P268_R 0.47 6.00E−06 0.000113 RASSF1_P244_F 1.53 0 0 TFF2_P178_F 0.96 9.00E−06 0.000163 TNFRSF10C_E109_F 1.06 0 0 CLDN4_P1120_R 0.82 9.00E−06 0.000164 AGTR1_P41_F 1.30 0 0 JAG2_P264_F 0.35 1.10E−05 0.000183 IRAK3_P13_F 1.44 0 0 MMP19_E274_R 0.75 1.20E−05 0.000198 TEK_E75_F 0.96 0 0 KRT13_P676_F 1.13 1.30E−05 0.000214 RIPK1_P868_F 1.16 0 0 MDR1_seq_42_S300_R 1.76 1.60E−05 0.000218 CDH13_P88_F 1.06 0 0 NOS2A_P288_R 0.76 1.60E−05 0.000218 THY1_P149_R 0.92 0 0 CLK1_P538_F 0.63 1.60E−05 0.000218 CHGA_E52_F 1.00 0 0 ER_seq_a1_S60_F 0.64 1.60E−05 0.000218 FRZB_E186_R 1.26 0 0 KRT5_P308_F 0.81 1.60E−05 0.000218 AGTR1_P154_F 1.10 0 0 CPA4_E20_F 0.80 1.60E−05 0.000218 EYA4_P794_F 1.11 0 0 SLC14A1_E295_F 1.34 0 0 GP1BB_P278_R 1.39 0 0 RARA_P1076_R 1.42 0 1.00E−06 SLIT2_E111_R 1.14 0 0 EGF_P413_F 1.09 0 1.00E−06 FGF3_E198_R 1.55 0 0 KRT13_P341_R 1.21 0 1.00E−06 STAT5A_P704_R 1.15 0 0 CSF1R_P73_F 0.92 0 1.00E−06 CDH11_E102_R 1.57 0 0 FGFR4_P610_F 0.89 0 2.00E−06 KRT13_P341_R 1.02 0 0 UGT1A1_P315_R 1.04 0 3.00E−06 FGF1_P357_R 0.92 0 0 STAT5A_P704_R 1.22 0 4.00E−06 SLIT2_P208_F 1.38 0 0 MAP3K1_P7_F 0.52 0 5.00E−06 EYA4_E277_F 1.30 0 0 IRF5_P123_F 0.35 0 6.00E−06 RASSF1_E116_F 1.63 0 0 RIPK1_P868_F 0.83 0 6.00E−06 HOXB2_P488_R 1.22 0 0 CSF1R_E26_F 1.01 0 7.00E−06 CSF3_P309_R 0.92 0 0 TEK_E75_F 1.09 0 7.00E−06 CDH13_E102_F 1.29 0 0 FGF1_P357_R 1.00 0 7.00E−06 HPN_P374_R 1.03 0 0 TRPM5_P979_F 1.20 0 7.00E−06 TNFRSF10C_P7_F 1.04 0 0 SNCG_E119_F 1.05 0 1.00E−05 TERT_P360_R 0.92 0 0 AATK_E63_R 1.25 1.00E−06 1.80E−05 HS3ST2_P171_F 1.25 0 0 SLC14A1_P369_R 1.15 1.00E−06 1.90E−05 SOX1_P294_F 1.20 0 0 FGF1_E5_F 0.91 1.00E−06 2.40E−05 TPEF_seq_44_S36_F 1.13 0 0 CSF2_P605_F 1.07 1.00E−06 2.50E−05 NTSR1_P318_F 1.21 0 0 HPN_P374_R 1.10 1.00E−06 3.00E−05 DES_E228_R 1.02 0 0 CSF3_P309_R 1.09 1.00E−06 3.40E−05 NOTCH4_E4_F 1.06 0 0 TMPRSS4_E83_F 0.99 2.00E−06 5.20E−05 FGF3_P171_R 1.29 0 0 AIM2_E208_F 0.60 3.00E−06 6.60E−05 GDF10_P95_R 1.19 0 0 AATK_P519_R 1.07 3.00E−06 6.80E−05 VIM_P343_R 1.26 0 0 CDH17_P376_F 0.95 4.00E−06 7.30E−05 MST1R_E42_R 1.01 0 0 MMP7_E59_F 0.62 4.00E−06 8.00E−05 GAS7_P622_R 1.17 0 0 THBS2_P605_R 0.87 4.00E−06 8.00E−05 VAV1_E9_F 1.08 0 0 KLK10_P268_R 0.47 6.00E−06 0.000113 RASSF1_P244_F 1.53 0 0 TFF2_P178_F 0.96 9.00E−06 0.000163 TNFRSF10C_E109_F 1.06 0 0 CLDN4_P1120_R 0.82 9.00E−06 0.000164 AGTR1_P41_F 1.30 0 0 JAG2_P264_F 0.35 1.10E−05 0.000183 IRAK3_P13_F 1.44 0 0 MMP19_E274_R 0.75 1.20E−05 0.000198 TEK_E75_F 0.96 0 0 KRT13_P676_F 1.13 1.30E−05 0.000214 RIPK1_P868_F 1.16 0 0 MDR1_seq_42_S300_R 1.76 1.60E−05 0.000218 CDH13_P88_F 1.06 0 0 NOS2A_P288_R 0.76 1.60E−05 0.000218 THY1_P149_R 0.92 0 0 CLK1_P538_F 0.63 1.60E−05 0.000218 CHGA_E52_F 1.00 0 0 ER_seq_a1_S60_F 0.64 1.60E−05 0.000218 FRZB_E186_R 1.26 0 0 KRT5_P308_F 0.81 1.60E−05 0.000218 AGTR1_P154_F 1.10 0 0 CPA4_E20_F 0.80 1.60E−05 0.000218 EYA4_P794_F 1.11 0 0 P2RX7_P597_F 0.97 1.80E−05 0.00024 NPY_E31_R 1.05 0 0 IRF7_E236_R 1.00 2.10E−05 0.000268 CDH11_P203_R 1.27 0 0 DUSP4_E61_F 0.42 2.20E−05 0.000274 HHIP_E94_F 1.11 0 0 SFTPA1_E340_R 0.96 2.20E−05 0.000274 GALR1_E52_F 1.19 0 0 HPN_P823_F 0.98 2.50E−05 0.000284 SFRP1_P157_F 1.25 0 0 HOXB2_P99_F 1.30 2.50E−05 0.000284 NPY_P295_F 1.21 0 0 TRIM29_E189_F 0.76 2.50E−05 0.000284 TMEFF2_E94_R 1.09 0 0 ACVR1C_P115_R 0.41 2.50E−05 0.000284 SFRP1_E398_R 1.56 0 0 CXCL9_E268_R 0.80 2.60E−05 0.000284 HOXB2_P99_F 1.09 0 0 HOXA5_E187_F 1.17 2.90E−05 0.000306 RARA_P1076_R 0.84 0 0 JAK3_P1075_R 0.74 2.90E−05 0.000306 DBC1_E204_F 1.07 0 0 FRZB_E186_R 1.16 3.20E−05 0.000327 PADI4_P1158_R 0.79 0 0 TUSC3_E29_R 0.89 3.20E−05 0.000327 NRG1_P558_R 1.18 0 0 PSCA_P135_F 0.76 3.30E−05 0.000329 PYCARD_P150_F 0.90 0 0 TFF1_P180_R 0.76 3.50E−05 0.000342 SLC5A8_E60_R 0.96 0 0 TRIM29_P135_F 0.70 3.80E−05 0.000365 MOS_E60_R 1.09 0 0 NBL1_P24_F 0.76 3.90E−05 0.000372 TERT_E20_F 1.03 0 0 RARA_P176_R 0.90 4.10E−05 0.000386 EYA4_P508_F 1.02 0 0 UGT1A1_E11_F 1.17 4.30E−05 0.000394 S100A4_E315_F 0.92 0 0 TSC2_E140_F 0.80 4.90E−05 0.000446 EPHA5_E158_R 1.07 0 0 CDH17_E31_F 0.91 5.20E−05 0.000459 TAL1_E122_F 1.11 0 0 SERPINB5_P19_R 0.86 5.30E−05 0.000459 SMO_E57_F 1.29 0 0 MBD2_P233_F 0.55 5.70E−05 0.000487 ISL1_E87_R 1.09 0 0 BMP2_P1201_F 0.71 5.80E−05 0.000493 LY6G6E_P45_R 0.82 0 0 SIN3B_P607_F −0.67 5.90E−05 0.000493 PALM2-AKAP2_P183_R 0.88 0 0 LY6G6E_P45_R 0.88 6.20E−05 0.000506 IRAK3_E130_F 1.28 0 0 CSF2_E248_R 0.81 6.40E−05 0.000506 TPEF_seq_44_S88_R 0.97 0 0 USP29_P282_R −0.34 6.40E−05 0.000506 MST1R_P392_F 1.04 0 0 SYK_P584_F 0.57 6.50E−05 0.000506 ETV1_P235_F 1.01 0 0 GPR116_E328_R 0.75 7.00E−05 0.000539 FLI1_P620_R 0.97 0 1.00E−06 SRC_P164_F 0.72 7.30E−05 0.000559 FGF1_E5_F 0.80 0 1.00E−06 FRK_P258_F 0.80 7.80E−05 0.000579 NTSR1_E109_F 1.28 0 1.00E−06 PTPN6_P282_R 0.66 7.80E−05 0.000579 HS3ST2_E145_R 0.93 0 1.00E−06 DDIT3_P1313_R 1.07 8.10E−05 0.000594 DIO3_P90_F 0.65 0 1.00E−06 SRC_E100_R 0.83 8.60E−05 0.000622 HTR1B_P222_F 1.24 0 1.00E−06 CALCA_P171_F 0.69 9.00E−05 0.000637 AATK_E63_R 0.86 0 1.00E−06 PTHR1_P258_F 0.57 9.30E−05 0.000654 GALR1_P80_F 1.07 0 1.00E−06 PCDH1_E22_F 0.15 9.50E−05 0.00066 TMEFF2_P152_R 0.93 0 1.00E−06 SPDEF_E116_R 0.74 9.60E−05 0.00066 STAT5A_E42_F 0.89 0 1.00E−06 NOS2A_E117_R 0.73 1.00E−04 0.000675 ISL1_P379_F 1.00 0 1.00E−06 MUC1_E18_R 0.55 0.000105 0.000702 IRAK3_P185_F 1.05 0 1.00E−06 ALOX12_E85_R 1.04 0.000114 0.00075 DLK1_E227_R 1.07 0 1.00E−06 TRIM29_P261_F 0.92 0.000117 0.000764 CSPG2_P82_R 0.79 0 1.00E−06 FRK_P36_F 0.84 0.00012 0.000775 FGFR4_P610_F 0.74 0 1.00E−06 NRG1_P558_R 1.44 0.000126 0.000803 POMC_P400_R 1.07 0 1.00E−06 HOXA5_P479_F 0.72 0.000128 0.000804 FLT4_E206_F 0.93 0 1.00E−06 ACVR1_P983_F 0.80 0.000131 0.000813 FLI1_E29_F 0.90 0 1.00E−06 HS3ST2_P171_F 1.20 0.000143 0.000879 THY1_P20_R 0.67 0 1.00E−06 IGFBP1_P12_R 0.85 0.000145 0.000881 SEPT9_P374_F 0.90 0 1.00E−06 ESR1_E298_R 0.70 0.000147 0.000882 EGF_P413_F 0.71 0 1.00E−06 SNCG_P53_F 0.85 0.000149 0.000884 CDH11_P354_R 0.89 0 1.00E−06 IGFBP1_E48_R 0.72 0.000153 9.00E−04 PDGFRB_P343_F 1.19 0 1.00E−06 TGFB3_E58_R 0.84 0.000171 0.000994 NOS2A_P288_R 0.72 0 2.00E−06 IGSF4_P86_R 1.08 0.000177 0.001019 MST1R_P87_R 0.83 0 2.00E−06 RHOH_P121_F −0.55 0.000192 0.001091 PENK_E26_F 0.80 0 2.00E−06 ACVR1_E328_R 1.10 0.000201 0.001127 FES_P223_R 1.09 0 2.00E−06 IL1RN_E42_F 0.72 0.000202 0.001127 HS3ST2_P546_F 0.84 0 2.00E−06 HLA-DOB_E432_R 0.50 0.000208 0.001149 DCC_P471_R 0.92 0 2.00E−06 BCR_P346_F 0.80 0.000228 0.001246 FRZB_P406_F 1.31 0 2.00E−06 GABRG3_P75_F −0.81 0.000231 0.001252 IGF2_P1036_R 0.81 0 2.00E−06 SEPT5_P464_R 0.81 0.00024 0.001283 MMP2_P197_F 0.75 0 2.00E−06 IGF1R_P325_R 0.17 0.000248 0.001302 CSF2_P605_F 0.88 0 2.00E−06 DAPK1_E46_R 0.61 0.000248 0.001302 WT1_E32_F 1.11 0 2.00E−06 NBL1_E205_R 0.71 0.00026 0.001346 BCR_P422_F 0.80 0 2.00E−06 PSCA_E359_F 0.75 0.000262 0.001346 IGFBP1_P12_R 0.87 1.00E−06 3.00E−06 PTPRO_P371_F 0.96 0.000264 0.001346 MT1A_P49_R 1.27 1.00E−06 3.00E−06 VAV1_P317_F 0.71 0.00027 0.001362 FABP3_P598_F 0.69 1.00E−06 3.00E−06 CHI3L2_E10_F −0.64 0.000278 0.001393 PRKCDBP_E206_F 1.08 1.00E−06 3.00E−06 CSPG2_P82_R 0.94 0.000295 0.00145 JAK3_E64_F 0.92 1.00E−06 3.00E−06 MOS_E60_R 1.10 0.000295 0.00145 UGT1A1_E11_F 0.92 1.00E−06 3.00E−06 MMP10_E136_R 0.69 0.000303 0.001478 TBX1_P520_F 0.70 1.00E−06 3.00E−06 EYA4_E277_F 1.04 0.000316 0.001524 IPF1_P750_F 1.07 1.00E−06 4.00E−06 NOTCH4_E4_F 0.94 0.000322 0.001541 KRT13_P676_F 0.95 1.00E−06 4.00E−06 WNT8B_P216_R −0.31 0.000331 0.001556 CD9_P504_F 0.67 1.00E−06 4.00E−06 AATK_P709_R 0.80 0.000331 0.001556 FLT1_P615_R 1.05 1.00E−06 5.00E−06 SFN_E118_F 0.67 0.000336 0.001564 HCK_P46_R 1.00 1.00E−06 5.00E−06 PLAT_P80_F 0.77 0.00034 0.001569 PTPRG_P476_F 1.20 1.00E−06 5.00E−06 VAMP8_P241_F 0.56 0.000357 0.001635 OPCML_E219_R 1.06 1.00E−06 5.00E−06 CEACAM1_P44_R 0.50 0.000372 0.001691 SLC5A5_E60_F 0.73 1.00E−06 5.00E−06 NEFL_P209_R 0.97 0.000378 0.001704 CSF3R_P8_F 0.77 1.00E−06 5.00E−06 COL18A1_P365_R 0.71 0.000384 0.001716 ASCL2_E76_R 0.92 1.00E−06 5.00E−06 SEPT5_P441_F 0.86 0.000387 0.001716 BMP4_P199_R 0.70 1.00E−06 5.00E−06 GJB2_P931_R 0.94 0.00039 0.001716 OPCML_P71_F 0.70 1.00E−06 5.00E−06 GUCY2D_E419_R 1.24 0.00041 0.001786 SPP1_E140_R 0.66 1.00E−06 5.00E−06 TERT_P360_R 0.82 0.000423 0.001822 ACVR1_E328_R 0.85 1.00E−06 5.00E−06 ZIM2_P22_F 0.58 0.000425 0.001822 MT1A_E13_R 0.83 1.00E−06 5.00E−06 PRSS8_E134_R 0.64 0.000441 0.001879 COL1A2_P48_R 1.07 1.00E−06 5.00E−06 NOS3_P38_F 0.65 0.000448 0.001882 WNT10B_P993_F 0.90 1.00E−06 6.00E−06 BCR_P422_F 0.81 0.000451 0.001882 VAV1_P317_F 0.74 1.00E−06 6.00E−06 PLAT_E158_F 0.73 0.000453 0.001882 CD9_P585_R 0.72 2.00E−06 6.00E−06 MAPK10_E26_F 0.93 0.00046 0.001897 WNT2_P217_F 0.99 2.00E−06 6.00E−06 HS3ST2_P546_F 0.82 0.000478 0.00196 SOX1_P1018_R 0.79 2.00E−06 7.00E−06 TRPM5_P721_F 0.64 0.000483 0.001962 IGFBP2_P306_F 1.15 2.00E−06 7.00E−06 DLL1_P832_F 0.76 0.000489 0.001974 CLK1_P538_F 0.65 2.00E−06 7.00E−06 CFTR_P372_R 0.91 5.00E−04 0.002003 FGF8_P473_F 0.95 2.00E−06 8.00E−06 FGFR3_E297_R 0.19 0.000513 0.002041 HTR1B_E232_R 0.80 2.00E−06 8.00E−06 NPR2_P1093_F −0.28 0.000535 0.002111 ALOX12_P223_R 0.83 2.00E−06 8.00E−06 USP29_P205_R −0.45 0.000552 0.002163 APBA2_P305_R 0.67 2.00E−06 9.00E−06 GABRA5_E44_R −0.62 0.000557 0.002166 TRPM5_P979_F 0.77 2.00E−06 9.00E−06 HOXB2_P488_R 1.04 0.000565 0.002183 RBP1_E158_F 0.90 3.00E−06 9.00E−06 CSPG2_E38_F 1.07 0.00058 0.002214 EPHA2_P340_R 0.79 3.00E−06 9.00E−06 S100A2_P1186_F 0.72 0.000584 0.002214 MYOD1_E156_F 0.86 3.00E−06 9.00E−06 VIM_P811_R 1.35 0.000585 0.002214 BCR_P346_F 0.72 3.00E−06 1.00E−05 IL1RN_P93_R 0.70 0.000599 0.002248 ALOX12_E85_R 0.81 3.00E−06 1.00E−05 BMP4_P199_R 0.73 0.000605 0.00225 FES_E34_R 0.99 3.00E−06 1.10E−05 LAT_E46_F −0.52 0.000607 0.00225 EPHA5_P66_F 0.82 3.00E−06 1.10E−05 IL12A_E287_R 0.24 0.000612 0.00225 NRG1_E74_F 0.92 3.00E−06 1.10E−05 HFE_E273_R 1.46 0.000635 0.002314 NTRK3_P752_F 0.88 3.00E−06 1.10E−05 AOC3_P890_R 0.72 0.000638 0.002314 ERG_E28_F 0.79 3.00E−06 1.20E−05 S100A4_E315_F 0.76 0.000645 0.002326 PLAT_E158_F 0.67 4.00E−06 1.20E−05 SERPINA5_P156_F 0.65 0.000669 0.002396 RARA_P176_R 0.77 4.00E−06 1.30E−05 CHI3L2_P226_F −0.61 0.00068 0.002419 MMP2_E21_R 0.92 4.00E−06 1.30E−05 IGSF4_P454_F 1.09 0.000715 0.002528 CCND2_P887_F 1.13 4.00E−06 1.30E−05 EVI2A_P94_R −1.06 0.000721 0.002532 MYH11_P236_R 1.09 4.00E−06 1.40E−05 TJP2_P330_R −0.77 0.00077 0.002686 NPY_P91_F 0.84 4.00E−06 1.40E−05 SPI1_P48_F 0.74 0.000776 0.002689 ETV1_P515_F 0.84 4.00E−06 1.40E−05 KRT5_E196_R 0.95 0.000803 0.002729 GUCY2D_E419_R 1.03 5.00E−06 1.50E−05 SYK_E372_F 0.27 0.000803 0.002729 GSTM2_P109_R 0.88 5.00E−06 1.50E−05 MFAP4_P10_R 0.53 0.000803 0.002729 WNT10B_P823_R 0.71 5.00E−06 1.60E−05 GLI2_P295_F 0.57 0.000808 0.002729 CCND2_P898_R 1.07 5.00E−06 1.60E−05 LIG3_P622_R 0.62 0.000818 0.002747 MDR1_seq_42_S300_R 1.03 5.00E−06 1.80E−05 FASTK_P598_R 0.51 0.000849 0.002834 GAS7_E148_F 1.19 6.00E−06 1.90E−05 FLJ20712_P984_R 0.63 0.000876 0.002877 ADCYAP1_P398_F 0.89 6.00E−06 2.00E−05 TAL1_E122_F 1.09 0.00088 0.002877 KRT5_E196_R 0.81 7.00E−06 2.10E−05 EPHA2_P340_R 0.63 0.000883 0.002877 RASGRF1_E16_F 1.17 8.00E−06 2.30E−05 HDAC1_P414_R 0.64 0.000883 0.002877 IGFBP7_P297_F 0.72 8.00E−06 2.30E−05 CD82_P557_R 0.67 0.000898 0.002898 SLC14A1_E295_F 0.66 8.00E−06 2.50E−05 TRIP6_P1090_F 0.79 0.000901 0.002898 TWIST1_E117_R 0.99 8.00E−06 2.50E−05 EYA4_P794_F 0.96 0.000912 0.002918 VIM_P811_R 0.95 9.00E−06 2.70E−05 PTK6_E50_F 0.57 0.000943 0.003 AATK_P519_R 0.73 9.00E−06 2.90E−05 APBA2_P305_R 0.62 0.000975 0.003083 GPR116_E328_R 0.63 1.00E−05 3.00E−05 NOTCH3_P198_R 0.59 0.001 0.003143 ASCL2_P360_F 1.17 1.00E−05 3.10E−05 TGFB2_E226_R 1.00 0.001012 0.003163 FGF2_P229_F 0.77 1.10E−05 3.10E−05 SH3BP2_E18_F 0.65 0.001021 0.003163 EPO_E244_R 1.06 1.10E−05 3.20E−05 ZIM3_E203_F −0.71 0.001024 0.003163 NID1_P714_R 0.67 1.10E−05 3.30E−05 FANCA_P1006_R −0.49 0.001071 0.003289 DIO3_P674_F 1.01 1.10E−05 3.30E−05 ABCG2_P178_R 0.23 0.001103 0.003368 ACVR1_P983_F 0.72 1.10E−05 3.30E−05 MMP9_P189_F 0.54 0.001125 0.003416 TFF2_P557_R 0.64 1.10E−05 3.30E−05 EPHA8_P456_R 0.64 0.001161 0.003487 DCC_E53_R 0.77 1.20E−05 3.60E−05 MAS1_P657_R −0.45 0.001166 0.003487 DDR2_P743_R 0.66 1.30E−05 3.60E−05 NID1_P714_R 0.68 0.001167 0.003487 MMP19_E274_R 0.64 1.30E−05 3.70E−05 KCNK4_E3_F 0.67 0.001203 0.003574 TP73_P945_F 0.81 1.40E−05 4.00E−05 CARD15_P302_R 0.77 0.00121 0.003574 NTRK2_P10_F 0.77 1.40E−05 4.10E−05 TNFRSF10C_P7_F 1.08 0.001222 0.00359 ISL1_P554_F 0.81 1.50E−05 4.10E−05 MCM2_P260_F −0.37 0.001257 0.003662 NGFB_E353_F 0.64 1.50E−05 4.10E−05 RUNX3_P247_F −0.65 0.00126 0.003662 TGFB2_E226_R 0.86 1.50E−05 4.20E−05 PADI4_E24_F 0.68 0.001363 0.003942 TWIST1_P44_R 0.74 1.50E−05 4.30E−05 SPP1_E140_R 0.62 0.001378 0.003963 ERN1_P809_R 0.75 1.60E−05 4.40E−05 ENC1_P484_R 0.13 0.001435 0.004106 MFAP4_P10_R 0.60 1.60E−05 4.40E−05 P2RX7_P119_R 0.55 0.001483 0.004221 HTR1B_P107_F 0.65 1.60E−05 4.40E−05 CD1A_P414_R −0.60 0.00153 0.004331 JAK3_P1075_R 0.56 1.70E−05 4.60E−05 CREBBP_P712_R 0.63 0.00154 0.004337 PADI4_E24_F 0.66 1.80E−05 4.80E−05 DBC1_E204_F 0.94 0.001559 0.004367 CFTR_P372_R 0.79 1.80E−05 4.90E−05 AXL_P223_R 0.76 0.00159 0.004403 GSTM2_E153_F 0.89 1.90E−05 5.00E−05 IRF7_P277_R 1.23 0.001594 0.004403 FGF12_E61_R 0.68 1.90E−05 5.10E−05 TRIP6_P1274_R 0.65 0.001596 0.004403 ADCYAP1_P455_R 0.83 1.90E−05 5.10E−05 CALCA_P75_F 1.00 0.001622 0.004452 ZIM2_E110_F 0.67 2.00E−05 5.30E−05 DNAJC15_P65_F −0.40 0.001669 0.004559 P2RX7_P597_F 0.63 2.10E−05 5.40E−05 GSTM2_P109_R 1.01 0.001702 0.004625 FHIT_P93_R 0.73 2.10E−05 5.40E−05 B3GALT5_P330_F −0.23 0.001783 0.004821 MFAP4_P197_F 0.66 2.20E−05 5.60E−05 TNFSF8_E258_R −0.57 0.00183 0.004922 CALCA_E174_R 0.85 2.30E−05 5.80E−05 GP1BB_P278_R 0.92 0.001852 0.004957 ABO_P312_F 0.90 2.30E−05 5.80E−05 EPHX1_P22_F 0.75 0.001879 0.005004 SLC14A1_P369_R 0.67 2.30E−05 5.80E−05 CD34_P780_R 0.52 0.001999 0.005271 CSF1R_P73_F 0.55 2.40E−05 6.10E−05 FLI1_P620_R 1.15 0.002008 0.005271 TMPRSS4_E83_F 0.62 2.40E−05 6.10E−05 CDK10_P199_R 0.48 0.002008 0.005271 FGF5_E16_F 0.76 2.50E−05 6.20E−05 EPHA2_P203_F 0.59 0.002061 0.005382 SCGB3A1_E55_R 0.87 2.70E−05 6.70E−05 RARB_E114_F 1.10 0.00207 0.005382 DBC1_P351_R 0.91 2.80E−05 7.00E−05 RET_seq_53_S374_F 1.38 0.002145 0.005528 HPN_P823_F 0.67 3.00E−05 7.40E−05 FGFR1_E317_F 0.26 0.002147 0.005528 PROK2_P390_F 1.13 3.10E−05 7.60E−05 NID1_P677_F 0.65 0.002322 0.005914 HOXA5_E187_F 0.81 3.20E−05 7.80E−05 NTSR1_P318_F 1.03 0.002322 0.005914 IGF2AS_E4_F 0.59 3.30E−05 8.00E−05 PPARD_P846_F 0.23 0.00233 0.005914 CSPG2_E38_F 0.79 3.40E−05 8.20E−05 TYRO3_P501_F 0.33 0.002348 0.005933 PDGFB_P719_F 0.64 3.40E−05 8.20E−05 LIF_E208_F 0.18 0.002518 0.006332 KRT5_P308_F 0.56 3.50E−05 8.50E−05 OGG1_E400_F 0.82 0.002721 0.006793 GDF10_E39_F 0.51 3.90E−05 9.20E−05 DDR1_P332_R 0.67 0.002726 0.006793 EPHA8_P456_R 0.67 3.90E−05 9.20E−05 FZD9_P15_R 0.52 0.002813 0.006977 P2RX7_P119_R 0.60 3.90E−05 9.30E−05 OPCML_E219_R 0.94 0.002874 0.00707 CALCA_P75_F 0.83 4.00E−05 9.30E−05 GAS7_P622_R 0.78 0.002877 0.00707 HHIP_P307_R 0.67 4.00E−05 9.40E−05 LTB4R_P163_F −0.31 0.002994 0.007325 MYOD1_P50_F 0.68 4.00E−05 9.40E−05 XRCC2_P1077_F 0.78 0.003061 0.007456 CPA4_E20_F 0.56 4.10E−05 9.60E−05 IRAK3_P13_F 1.15 0.003093 0.007499 SOX17_P287_R 0.77 4.70E−05 0.000107 ACVR1C_P363_F 0.74 0.003161 0.007603 IRF7_E236_R 0.77 4.70E−05 0.000107 DHCR24_P652_R −0.50 0.003164 0.007603 USP29_E274_F −0.66 4.70E−05 0.000108 PADI4_P1158_R 0.55 0.003183 0.007615 DLC1_P88_R −0.67 4.80E−05 0.00011 NTSR1_E109_F 1.16 0.003202 0.007627 GFI1_P45_R 0.89 4.90E−05 0.000111 SLC5A8_E60_R 0.76 0.003305 0.007838 FGF12_P210_R 0.91 4.90E−05 0.000111 RASSF1_E116_F 1.41 0.003345 0.007897 AHR_E103_F 0.55 5.00E−05 0.000113 IGSF4C_P533_R 0.31 0.003408 0.007973 FLT1_E444_F 1.12 5.10E−05 0.000113 IL3_P556_F −0.30 0.003418 0.007973 S100A2_E36_R 0.51 5.10E−05 0.000114 THBS1_E207_R 0.25 0.003421 0.007973 PLXDC2_E337_F 1.19 5.20E−05 0.000116 SMO_E57_F 1.45 0.003478 0.00804 IFNGR2_E164_F 0.40 5.30E−05 0.000118 PTPRH_P255_F 0.68 0.00348 0.00804 MMP9_P189_F 0.51 5.40E−05 0.000118 SEMA3B_P110_R 0.37 0.003504 0.00804 RBP1_P150_F 0.91 6.00E−05 0.000132 DST_E31_F 0.29 0.003509 0.00804 HOXA5_P1324_F 0.59 6.10E−05 0.000134 NPR2_P618_F −0.57 0.003548 0.008094 TBX1_P885_R 0.83 6.50E−05 0.000142 SRC_P297_F 0.55 0.003612 0.008206 PENK_P447_R 0.74 6.60E−05 0.000144 RIPK4_E166_F 0.41 0.003629 0.00821 UGT1A1_P315_R 0.58 6.90E−05 0.00015 SOX1_P294_F 0.86 0.003691 0.008316 COMT_E401_F 0.68 7.00E−05 0.000151 FGF3_P171_R 0.95 0.003789 0.008501 CD34_P780_R 0.50 7.80E−05 0.000167 GUCY2D_P48_R 0.60 0.003852 0.008606 PALM2-AKAP2_P420_R 0.72 7.90E−05 0.000168 ALOX12_P223_R 0.74 0.003947 0.008781 GJB2_P791_R 0.97 8.00E−05 0.000169 CASP10_P186_F 0.41 0.003998 0.008859 KDR_P445_R 0.88 8.10E−05 0.000171 HS3ST2_E145_R 0.80 0.004033 0.0089 KCNK4_P171_R 0.55 8.10E−05 0.000171 HRASLS_P353_R 0.50 0.004141 0.009101 TMPRSS4_P552_F 0.71 8.50E−05 0.000177 ITGB4_E144_F 0.15 0.00417 0.009128 TUBB3_E91_F 0.59 8.80E−05 0.000184 FGF3_E198_R 1.08 0.004212 0.009183 PLA2G2A_P528_F 0.50 8.80E−05 0.000184 TUBB3_E91_F 0.70 0.004288 0.009297 TNF_P158_F 0.66 8.90E−05 0.000185 NRG1_E74_F 0.90 0.004325 0.009297 PDGFRB_P273_F 0.56 9.10E−05 0.000187 SNCG_P98_R 0.45 0.004329 0.009297 MEG3_E91_F 0.60 9.10E−05 0.000187 ZIM2_E110_F 0.40 0.004333 0.009297 GLI2_P295_F 0.60 9.40E−05 0.000193 JAK3_E64_F 0.98 0.004648 0.009932 POMC_E254_F 0.64 9.50E−05 0.000194 TNFRSF10C_E109_F 0.92 0.004696 0.009937 FLT3_P302_F 0.98 9.70E−05 0.000198 DES_P1006_R 0.43 0.004698 0.009937 IL18BP_P51_R 0.51 0.000105 0.000213 FGF2_P229_F 0.80 0.004705 0.009937 RARB_E114_F 0.84 0.000107 0.000215 CAPG_E228_F 0.42 0.00487 0.01021 SLC5A8_P38_R 0.77 0.000112 0.000226 MYCN_E77_R 0.21 0.004885 0.01021 IGFBP2_P353_R 0.61 0.000117 0.000234 NOTCH1_P1198_F 0.50 0.004895 0.01021 TNFRSF1A_P678_F 0.53 0.000124 0.000246 EVI2A_E420_F −0.44 0.00491 0.01021 PTPRO_E56_F 1.04 0.000124 0.000246 HLA-DOA_P191_R 0.44 0.005032 0.010388 PYCARD_P393_F 0.52 0.00013 0.000256 GALR1_E52_F 0.88 0.005034 0.010388 TRIM29_P261_F 0.59 0.000131 0.000258 VIM_P343_R 1.02 0.005107 0.0105 SEZ6L_P249_F 0.86 0.000134 0.000263 TNFRSF1A_P678_F 0.53 0.00523 0.010712 PLAT_P80_F 0.69 0.000141 0.000275 TPEF_seq_44_S88_R 0.84 0.00531 0.010833 ADAMTS12_E52_R 0.68 0.000141 0.000275 NEU1_P745_F −0.78 0.005491 0.01114 CSF2_E248_R 0.59 0.000144 0.00028 ETV6_E430_F 0.28 0.005501 0.01114 IRF7_P277_R 0.95 0.000155 0.000299 POMC_P53_F 1.26 0.005539 0.011174 GUCY2D_P48_R 0.53 0.00017 0.000327 CDH13_E102_F 0.98 0.005561 0.011177 NBL1_P24_F 0.60 0.000178 0.00034 SLIT2_E111_R 0.73 0.005597 0.011207 HLA-F_E402_F 1.02 0.00018 0.000343 MST1R_E42_R 0.77 0.005629 0.011231 ALK_E183_R 0.52 0.00018 0.000343 MLH3_P25_F 0.29 0.005687 0.011279 NEFL_P209_R 0.69 0.000182 0.000345 WNT10B_P823_R 0.64 0.005697 0.011279 ADCYAP1_E163_R 0.79 0.000185 0.00035 HIC2_P498_F 0.65 0.005716 0.011279 TRIP6_P1090_F 0.57 0.000192 0.000361 SHH_E328_F 0.48 0.005914 0.011628 SLC22A3_E122_R 0.66 0.000206 0.000387 IGF2AS_E4_F 0.48 0.00609 0.01193 MAPK10_E26_F 0.66 0.000207 0.000388 ASCL2_E76_R 0.53 0.006115 0.011936 ST6GAL1_P164_R 0.71 0.000215 4.00E−04 IGFBP3_P1035_F −1.23 0.006172 0.012004 PTPRO_P371_F 0.63 0.000216 4.00E−04 CASP10_P334_F 0.46 0.006233 0.012018 EPHA7_E6_F 0.87 0.000223 0.000412 ERG_E28_F 0.71 0.006241 0.012018 KCNK4_E3_F 0.54 0.000224 0.000412 POMC_P400_R 0.97 0.006251 0.012018 ABO_E110_F 0.76 0.000225 0.000412 SFTPC_E13_F 0.43 0.006268 0.012018 TYRO3_P501_F 0.30 0.000225 0.000412 SPI1_P929_F 0.37 0.006441 0.012305 APC_P14_F 0.68 0.000231 0.000421 MET_E333_F 0.71 0.006491 0.012358 CSF1_P339_F 0.72 0.000241 0.000437 LMO1_E265_R 0.63 0.00661 0.01254 HLF_E192_F 0.74 0.000242 0.000438 CCND1_P343_R 0.45 0.006714 0.012693 PDE1B_E141_F 0.55 0.000254 0.000458 CTGF_E156_F 0.51 0.006824 0.012855 SMO_P455_R 0.71 0.000261 0.000469 THY1_P149_R 0.76 0.007039 0.013197 SEMA3C_P642_F −0.72 0.000263 0.000471 CCL3_E53_R −0.52 0.007054 0.013197 MATK_P64_F 0.67 0.000266 0.000475 TFF2_P557_R 0.52 0.007133 0.013298 DAB2IP_E18_R 0.59 0.000286 0.000508 COL1A2_P48_R 0.98 0.007212 0.013319 FLT1_P302_F 0.74 0.000292 0.000517 TMPRSS4_P552_F 0.59 0.007217 0.013319 MYH11_P22_F 0.72 0.000296 0.000523 CALCA_E174_R 0.80 0.007218 0.013319 SYK_P584_F 0.48 0.000297 0.000523 ABCC5_P444_F 0.30 0.00728 0.013388 SFTPA1_E340_R 0.63 0.000309 0.00054 MST1R_P87_R 0.69 0.007334 0.013418 MMP9_P237_R 0.65 0.000309 0.00054 FRZB_P406_F 1.13 0.007346 0.013418 AXL_P223_R 0.58 0.000322 0.00056 TK1_P62_R 0.11 0.007378 0.013432 DHCR24_P652_R −0.45 0.000326 0.000566 AFF3_P808_F −0.50 0.007428 0.013477 GABRG3_P75_F −0.56 0.00033 0.000572 PLXDC1_P236_F 0.49 0.00753 0.013616 AATK_P709_R 0.62 0.000335 0.000577 NPY_E31_R 0.71 0.00756 0.013625 KLK10_P268_R 0.50 0.000337 0.000579 DDR2_P743_R 0.56 0.007795 0.014003 IL1RN_P93_R 0.55 0.000367 0.000629 CHD2_P667_F −0.41 0.007831 0.014008 TMEFF1_P626_R 0.44 0.000371 0.000633 ERCC6_P698_R 0.31 0.00785 0.014008 PTHR1_P258_F 0.45 0.000385 0.000656 TP73_P496_F 0.81 0.007926 0.014084 NTRK3_E131_F 0.88 0.000393 0.000667 NPY_P295_F 0.80 0.007945 0.014084 EPHA2_P203_F 0.53 0.000398 0.000673 GSTM2_E153_F 0.87 0.008072 0.014263 FAS_P322_R 0.53 0.00041 0.00069 CTSD_P726_F 0.37 0.008135 0.014289 PDGFRB_E195_R 0.79 0.000421 0.000707 MC2R_P1025_F −0.46 0.00814 0.014289 CSF1R_E26_F 0.56 0.000445 0.000744 GRB10_E85_R 0.65 0.008269 0.014468 MATK_P190_R 0.59 0.000453 0.000756 MMP19_P306_F 0.47 0.008308 0.01449 FLT4_P180_R 0.87 0.000459 0.000763 ERBB4_P541_F 0.30 0.008526 0.014782 DAB2IP_P9_F 0.63 0.000462 0.000765 HLA-DQA2_P282_R −0.47 0.00853 0.014782 FGFR3_E297_R 0.35 0.000463 0.000765 EPHB2_E297_F 0.16 0.00868 0.014971 OAT_P465_F 0.60 0.000489 0.000805 PPARG_E178_R 0.14 0.00872 0.014971 TAL1_P594_F 0.63 0.000497 0.000816 DAPK1_P345_R 0.39 0.008722 0.014971 FGF5_P238_R 0.66 0.000509 0.000834 ITK_E166_R −0.58 0.009097 0.015564 COL1A2_E299_F 0.59 0.000513 0.000835 HIC-1_seq_48_S103_R −0.83 0.009187 0.015648 CYP1B1_E83_R 0.73 0.000514 0.000835 RIPK3_P124_F 0.47 0.009219 0.015648 SOX17_P303_F 0.54 0.000515 0.000835 DNMT3B_P352_R 0.46 0.009232 0.015648 TFPI2_P9_F 0.85 0.000526 0.00085 PYCARD_P150_F 0.40 0.009323 0.015746 ZIM2_P22_F 0.56 0.000531 0.000854 CEACAM1_E57_R 0.27 0.009348 0.015746 NGFB_P13_F 0.55 0.000532 0.000854 BMPR2_E435_F −0.15 0.009388 0.015763 ALPL_P433_F 0.46 0.000563 0.000901 TMEFF2_P152_R 0.67 0.009456 0.015828 DNAJC15_E26_R 0.50 0.000565 0.000903 TJP2_P518_F −0.63 0.009504 0.015859 PTPRG_E40_R 0.66 0.000576 0.000917 IGF1R_E186_R 0.14 0.009681 0.016105 SPARC_E50_R 0.49 6.00E−04 0.000953 GSTM2_P453_R 0.52 0.010076 0.016712 RARB_P60_F 0.57 0.000606 0.000959 CRK_P721_F 0.38 0.010547 0.017439 TGFB1_P833_R 0.68 0.000632 0.000997 SEZ6L_P249_F 1.26 0.010599 0.017471 ER_seq_a1_S60_F 0.54 0.000647 0.001017 SEZ6L_P299_F 1.03 0.01072 0.017584 ESR1_E298_R 0.59 0.000649 0.001018 EPO_P162_R 0.57 0.010732 0.017584 PAX6_P1121_F 0.58 0.000672 0.00105 TP73_P945_F 0.70 0.010906 0.017732 GJB2_P931_R 0.56 0.000694 0.001078 MYCN_P464_R 0.15 0.010912 0.017732 BMP6_P163_F 0.41 0.000694 0.001078 ZMYND10_E77_R 0.82 0.010921 0.017732 THBS2_P605_R 0.46 0.000714 0.001106 SPDEF_P6_R 0.47 0.011096 0.017963 SNCG_E119_F 0.60 0.000743 0.001146 IL1B_P582_R 0.42 0.011184 0.018051 FGF8_E183_F 0.45 0.000784 0.001207 TGFA_P642_R 0.29 0.01128 0.018152 ERBB4_P541_F 0.71 0.000789 0.001211 AGTR1_P154_F 0.97 0.011348 0.018206 TRPM5_P721_F 0.51 0.00083 0.001269 ZIM3_P718_R −0.52 0.011472 0.01835 CRIP1_P874_R 0.55 0.000832 0.001269 EPHA1_P119_R 0.34 0.011569 0.018451 ST6GAL1_P528_F 0.66 0.000843 0.001282 MMP3_P16_R −0.63 0.011975 0.018993 HOXA5_P479_F 0.58 0.000949 0.001439 MKRN3_P108_F −0.51 0.012043 0.018993 DLC1_E276_F −0.56 0.000965 0.00146 IGFBP2_P353_R 0.65 0.012048 0.018993 CASP6_P230_R 0.13 0.000981 0.001479 IGFBP6_E47_F 0.25 0.012049 0.018993 PLAU_P176_R 0.63 0.001004 0.001509 OAT_P465_F 0.79 0.01212 0.01905 GRB10_P496_R 0.49 0.001013 0.001519 SNRPN_P230_R −0.29 0.012181 0.019089 GABRB3_E42_F 0.71 0.001039 0.001554 IRAK3_P185_F 0.86 0.012261 0.019159 ADAMTS12_P250_R 0.80 0.001045 0.001555 KCNQ1_P546_R 0.32 0.012354 0.019249 CDK6_P291_R 0.73 0.001046 0.001555 ZNFN1A1_P179_F −0.61 0.012828 0.01993 F2R_P88_F 0.67 0.001067 0.001581 PHLDA2_P622_F 0.40 0.012907 0.019996 GP1BB_E23_F 0.77 0.001108 0.001637 RASSF1_P244_F 1.17 0.013027 0.020091 SERPINE1_P519_F 0.51 0.001171 0.001725 EDN1_E50_R 0.26 0.013057 0.020091 IGFBP7_P371_F 0.74 0.00123 0.001806 SEMA3A_P658_R 0.40 0.01312 0.020091 TSP50_P137_F 0.58 0.001233 0.001806 MYOD1_E156_F 0.74 0.013135 0.020091 CCKBR_P480_F 0.69 0.001238 0.001809 WNT1_E157_F 0.51 0.013155 0.020091 TIMP3_seq_7_S38_F 0.79 0.001286 0.001873 EFNB3_P442_R 0.24 0.013228 0.020146 RET_seq_53_S374_F 0.69 0.00129 0.001874 GLI3_E148_R −0.29 0.013362 0.020294 CDKN1C_P626_F 0.72 0.001368 0.001982 PROK2_E0_F 0.34 0.013429 0.020338 S100A4_P194_R 0.55 0.001423 0.002056 ERCC1_P440_R 0.26 0.01364 0.020601 GPX3_E178_F 0.48 0.001445 0.002081 SLC22A18_P472_R −0.35 0.013803 0.020789 BDNF_E19_R 0.54 0.001477 0.002121 BCAM_P205_F 0.24 0.013845 0.020793 NID1_P677_F 0.48 0.001484 0.002126 MGMT_P281_F 0.21 0.013994 0.020959 ALK_P28_F 0.58 0.001564 0.002235 TSP50_P137_F 0.72 0.01416 0.021149 TIMP2_P267_F 0.62 0.001581 0.002252 S100A2_E36_R 0.34 0.014233 0.0212 MKRN3_E144_F −0.63 0.001654 0.00235 HIC2_P528_R 0.60 0.014667 0.021786 KIT_P405_F 0.64 0.001667 0.002356 MATK_P64_F 0.62 0.014749 0.021848 SERPINA5_P156_F 0.47 0.001667 0.002356 IGFBP3_P423_R −0.89 0.015111 0.022323 PTPNS1_P301_R 0.26 0.001675 0.00236 EPO_E244_R 0.92 0.015167 0.022344 PSCA_E359_F 0.38 0.0017 0.002389 ZAP70_P220_R 0.37 0.015505 0.022781 FGFR1_E317_F 0.37 0.001829 0.002562 CTNNA1_P382_R 0.16 0.015835 0.023202 SEMA3B_E96_F 0.41 0.001857 0.002595 GLI3_P453_R 0.67 0.015961 0.023324 PTPRH_E173_F 0.39 0.001905 0.002655 NPY_P91_F 0.73 0.016488 0.023972 PYCARD_E87_F 0.70 0.00213 0.002961 WNT2_P217_F 0.73 0.016494 0.023972 SEZ6L_P299_F 0.69 0.002141 0.002967 IRAK3_E130_F 0.94 0.01675 0.024232 PLXDC1_P236_F 0.59 0.002195 0.003033 EVI1_E47_R 0.34 0.016762 0.024232 KDR_E79_F 0.72 0.002203 0.003033 TNFRSF10D_P70_F 0.81 0.016837 0.024276 CCNA1_E7_F 0.61 0.002205 0.003033 RBL2_P250_R 0.65 0.017001 0.024414 GABRB3_P92_F 0.37 0.00225 0.003086 RARRES1_E235_F 0.57 0.017066 0.024414 TDGF1_E53_R 0.45 0.002303 0.003151 KCNQ1_E349_R 0.19 0.017069 0.024414 PDGFRA_P1429_F 0.56 0.002313 0.003156 TNFRSF10D_E27_F 0.88 0.017209 0.02455 TNFRSF10D_E27_F 0.67 0.002323 0.00316 TERT_E20_F 0.55 0.017478 0.024867 CD40_E58_R 0.61 0.002373 0.003216 CCKBR_P480_F 0.88 0.01756 0.024919 ERCC1_P354_F 0.36 0.002376 0.003216 EIF2AK2_P313_F 0.75 0.017937 0.025388 LOX_P313_R 0.52 0.002384 0.003218 PWCR1_P811_F −0.34 0.018089 0.025536 PTHLH_P757_F 0.47 0.002587 0.003483 MMP2_P197_F 0.60 0.018265 0.025718 PTHLH_E251_F 0.42 0.002617 0.003515 NR2F6_E375_R 0.22 0.018646 0.026125 ASCL1_E24_F 0.68 0.002661 0.003565 PROK2_P390_F 1.04 0.018651 0.026125 ESR2_P162_F 0.47 0.00268 0.003581 LMO2_E148_F −0.37 0.018754 0.026201 ETV6_E430_F 0.34 0.002703 0.003602 PWCR1_E81_R −0.35 0.018978 0.026445 AIM2_P624_F 0.47 0.00274 0.003642 SLC5A8_P38_R 0.69 0.01934 0.026881 MAPK12_P416_F 0.65 0.002839 0.003764 PKD2_P287_R 0.22 0.019444 0.026956 TJP1_P390_F 0.26 0.002896 0.00383 NCL_P840_R 0.32 0.019571 0.027063 TCF4_P175_R 0.61 0.002905 0.003831 SEMA3C_P642_F −0.69 0.019762 0.027257 TGFB2_P632_F 0.53 0.002937 0.003864 HLA-DPA1_P205_R 0.39 0.019914 0.027397 HHIP_P578_R 0.42 0.003045 0.003996 PLA2G2A_P528_F 0.39 0.020022 0.027476 FN1_E469_F 0.56 0.003075 0.004025 ADCYAP1_P455_R 0.74 0.020101 0.027514 NKX3-1_P871_R 0.59 0.003119 0.004073 FLT3_P302_F 0.95 0.020613 0.028143 RIPK3_P124_F 0.45 0.003205 0.004174 MFAP4_P197_F 0.46 0.021039 0.028585 GLI3_P453_R 0.49 0.003248 0.004219 GRB7_P160_R 0.44 0.021042 0.028585 GSTP1_E322_R 0.55 0.003389 0.004392 SPP1_P647_F 0.42 0.021458 0.029077 CFTR_P115_F 0.63 0.003481 0.004499 HIC1_P565_R 0.36 0.021589 0.029181 IGF2AS_P203_F 0.54 0.003498 0.00451 BAX_E281_R 0.28 0.021791 0.029381 MMP7_E59_F 0.35 0.003553 0.004569 RBP1_E158_F 0.86 0.021932 0.029497 BDNF_P259_R 0.49 0.003576 0.004587 FES_E34_R 0.59 0.022293 0.029908 SIN3B_P607_F −0.54 0.00372 0.004761 THPO_E483_F 0.53 0.022367 0.029933 COL18A1_P494_R 0.54 0.00378 0.004826 MCM2_P241_R 0.12 0.022646 0.030233 SIN3B_P514_R −0.49 0.0038 0.004839 PDGFA_P841_R 0.13 0.022757 0.030302 EPO_P162_R 0.45 0.0041 0.005208 ERBB4_P255_F 0.18 0.022811 0.030302 IL6_P213_R 0.57 0.00411 0.005208 GP1BB_E23_F 0.95 0.022968 0.030436 SPI1_P48_F 0.48 0.004143 0.005237 H19_P1411_R −0.44 0.023139 0.030588 PAX6_E129_F 0.54 0.004195 0.005288 ICA1_P72_R 0.21 0.023645 0.031181 MEG3_P235_F 0.52 0.004204 0.005288 RIPK3_P24_F 0.60 0.023783 0.031287 PAX6_P50_R 0.74 0.004227 0.005304 SLC22A3_E122_R 0.75 0.023878 0.031335 CCKBR_P361_R 0.35 0.004309 0.005394 LRRK1_P39_F −0.15 0.024169 0.031588 LCN2_P141_R 0.43 0.004335 0.005413 OPCML_P71_F 0.47 0.024187 0.031588 HCK_P858_F 0.53 0.004364 0.005432 RARRES1_P426_R 0.50 0.024386 0.031699 PLA2G2A_E268_F 0.42 0.004379 0.005432 CDC25B_E83_F 1.15 0.02439 0.031699 HLA-DOB_E432_R 0.43 0.004382 0.005432 DIO3_P674_F 0.83 0.024504 0.031772 COL1A1_P5_F 0.43 0.004482 0.005543 IGF1_E394_F 0.51 0.024884 0.032187 DAPK1_E46_R 0.48 0.004527 0.005585 COL1A1_P5_F 0.39 0.025346 0.032705 SLC22A3_P634_F 0.44 0.00464 0.005711 LIF_P383_R 0.41 0.025406 0.032705 GABRA5_E44_R −0.41 0.004665 0.005728 TMEFF2_P210_R 0.51 0.025546 0.032808 EPHA8_P256_F 0.42 0.004698 0.005755 ERBB3_E331_F 0.30 0.026136 0.033486 PTCH2_P37_F 0.47 0.004735 0.005787 HBII-13_P991_R −0.22 0.026361 0.033621 SEMA3A_P658_R 0.41 0.004786 0.005835 GDF10_E39_F 0.32 0.026366 0.033621 RARA_E128_R 0.58 0.004928 0.005994 APC_E117_R 0.66 0.026452 0.033651 AKT1_P310_R 0.43 0.00508 0.006165 CRIP1_P874_R 0.54 0.026665 0.033843 EPHX1_P22_F 0.53 0.005127 0.006206 PPARG_P693_F 0.47 0.027004 0.034192 SLC22A3_P528_F 0.48 0.00518 0.006256 CEBPA_P1163_R 0.71 0.027096 0.034229 IGFBP6_E47_F 0.31 0.005329 0.006421 THY1_P20_R 0.42 0.027397 0.034528 TIAM1_P188_R 0.77 0.005387 0.006476 IHH_E186_F 0.77 0.027529 0.034537 RAP1A_P285_R 0.32 0.005402 0.006479 EYA4_P508_F 0.64 0.027532 0.034537 DLL1_P832_F 0.44 0.00549 0.006568 MAD2L1_E93_F −0.35 0.027652 0.034608 IGFBP6_P328_R 0.46 0.005651 0.006746 ESR1_P151_R −0.60 0.027742 0.03464 IGSF4_P86_R 0.50 0.00572 0.006813 SMO_P455_R 0.69 0.028217 0.035152 PTPN6_P282_R 0.40 0.00584 0.006939 HTR1B_P222_F 0.84 0.028532 0.035463 HRASLS_P353_R 0.42 0.005883 0.006974 MYH11_P236_R 0.90 0.028843 0.035768 PGR_P456_R −0.48 0.005954 0.007043 CD9_P504_F 0.48 0.029576 0.036593 POMC_P53_F 0.69 0.006015 0.007098 BMP6_P163_F 0.46 0.029756 0.036731 DST_E31_F 0.19 0.006063 0.007139 MT1A_P49_R 1.08 0.03012 0.037096 MT1A_P600_F 0.45 0.006136 0.007208 WT1_E32_F 0.77 0.030345 0.037288 CALCA_P171_F 0.41 0.006216 0.007286 NEFL_E23_R 0.56 0.030443 0.037307 MOS_P746_F −0.43 0.006544 0.007653 PITX2_E24_R −0.64 0.030499 0.037307 FGFR3_P1152_R 0.44 0.006586 0.007684 CDKN1C_P6_R 0.26 0.030577 0.037318 NTRK3_P636_R 0.45 0.006624 0.007707 GFI1_P208_R 0.51 0.03071 0.037397 APC_P280_R 0.68 0.006641 0.007707 UGT1A7_P751_R −0.21 0.030838 0.037467 FGFR1_P204_F 0.52 0.00665 0.007707 CDH11_P203_R 0.78 0.030907 0.037468 APBA2_P227_F 0.51 0.006719 0.007769 SFRP1_E398_R 0.87 0.031601 0.038223 AIM2_E208_F 0.35 0.006779 0.007821 HHIP_E94_F 0.68 0.032125 0.03877 ITK_E166_R −0.51 0.006934 0.007982 KRAS_P651_F 0.15 0.032252 0.038777 WNT5A_E43_F 0.36 0.006957 0.00799 APBA2_P227_F 0.52 0.032335 0.038777 TMEFF2_P210_R 0.47 0.0072 0.008252 IL2_P607_R 0.42 0.032412 0.038777 ATP10A_P524_R −0.45 0.007285 0.008314 IGF2AS_P203_F 0.55 0.032418 0.038777 DDR1_P332_R 0.45 0.007298 0.008314 TWIST1_P44_R 0.57 0.032571 0.038866 NGFR_P355_F 0.33 0.007303 0.008314 PXN_P308_F 0.37 0.032688 0.038866 FLT3_E326_R 0.44 0.007345 0.008344 SOX1_P1018_R 0.53 0.032708 0.038866 HIC1_P565_R 0.43 0.007472 0.008469 MMP14_P208_R 0.40 0.033065 0.039204 DAB2_P468_F 0.60 0.007537 0.008519 SOX17_P303_F 0.58 0.033301 0.039398 CCL3_E53_R −0.35 0.007549 0.008519 PTPRH_E173_F 0.30 0.03371 0.039795 CDKN1A_E101_F 0.23 0.007647 0.008609 WNT10B_P993_F 0.57 0.033831 0.039812 RET_seq_54_S260_F 0.68 0.007662 0.008609 APC_P14_F 0.72 0.033872 0.039812 TFF1_P180_R 0.37 0.007776 0.008717 FGFR3_P1152_R 0.56 0.034258 0.040179 CTSH_E157_R 0.38 0.007798 0.008724 MATK_P190_R 0.51 0.035204 0.041199 PODXL_P1341_R 0.52 0.008171 0.009121 PTCH_E42_F 0.10 0.035801 0.041769 NOS2A_E117_R 0.37 0.008444 0.009405 TMEFF2_E94_R 0.55 0.035846 0.041769 HBII-52_E142_F −0.38 0.008909 0.009902 F2R_P88_F 0.59 0.036384 0.042305 ALPL_P278_F 0.62 0.009035 0.01002 FGF7_P44_F 0.37 0.036622 0.04249 GSTM2_P453_R 0.42 0.009119 0.010091 IGF2R_P396_R 0.18 0.036818 0.042626 TWIST1_P355_R 0.42 0.009166 0.010122 IGFBP2_P306_F 0.88 0.036939 0.042627 ASCL1_P747_F 0.44 0.009228 0.010169 EGF_E339_F −0.50 0.036976 0.042627 NTRK1_E74_F −0.57 0.009314 0.010242 PLAGL1_E68_R −0.31 0.03719 0.042782 SRC_P164_F 0.34 0.00965 0.010582 TNFRSF10A_P91_F 0.29 0.037318 0.042838 IGF1R_P325_R 0.25 0.009682 0.010582 VAV1_E9_F 0.65 0.038001 0.043529 EVI1_E47_R 0.61 0.009701 0.010582 CD9_P585_R 0.56 0.038414 0.043878 KCNQ1_P546_R 0.31 0.009706 0.010582 WRN_P969_F 0.58 0.038488 0.043878 CHGA_P243_F 0.34 0.01015 0.011043 WNT5A_P655_F −0.36 0.038548 0.043878 DSP_P440_R 0.32 0.010375 0.011264 MMP9_E88_R 0.51 0.038723 0.043944 IL1A_E113_R 0.66 0.010474 0.011348 TM7SF3_P1068_R −0.74 0.038769 0.043944 SNURF_E256_R −0.38 0.010502 0.011354 CDC258_P11_R 0.78 0.039064 0.044186 ZMYND10_E77_R 0.65 0.010572 0.011406 CTLA4_E176_R −0.38 0.039978 0.045072 SERPINB5_P19_R 0.36 0.0108 0.011627 CFTR_P115_F 0.69 0.040014 0.045072 AOC3_P890_R 0.37 0.010938 0.011752 EXT1_E197_F 0.24 0.040223 0.045199 SEPT5_P464_R 0.39 0.010967 0.011758 SNRPN_seq_18_S99_F −0.25 0.040294 0.045199 DES_P1006_R 0.37 0.011013 0.011783 GABRB3_P92_F 0.46 0.041102 0.046009 BMP2_E48_R 0.50 0.01106 0.011809 ASCL2_P360_F 0.58 0.041234 0.046062 SNCG_P53_F 0.44 0.011246 0.011983 PLXDC2_E337_F 0.95 0.041511 0.046137 SGCE_E149_F 0.59 0.011283 0.011997 PDGFB_P719_F 0.46 0.041514 0.046137 TFF2_P178_F 0.36 0.011496 0.012199 ADAMTS12_P250_R 1.20 0.041557 0.046137 MBD2_P233_F 0.35 0.011773 0.012467 HTR1B_E232_R 0.58 0.041957 0.046486 ZAP70_P220_R 0.36 0.01189 0.012565 TNK1_P41_R 0.42 0.042059 0.046503 COL4A3_E205_R 0.38 0.011971 0.012624 COL1A2_E299_F 0.60 0.042566 0.046845 TGFB3_E58_R 0.35 0.012335 0.012982 ONECUT2_P315_R 0.87 0.042612 0.046845 TFPI2_P152_R 0.53 0.012701 0.01334 MEG3_E91_F 0.34 0.042628 0.046845 IL17RB_E164_R 0.55 0.012728 0.013341 MAPK12_E165_R 0.20 0.043194 0.047325 MCAM_P265_R 0.42 0.012858 0.01345 MT1A_E13_R 0.61 0.043243 0.047325 MMP19_P306_F 0.35 0.012896 0.013463 TMEFF1_P626_R 0.28 0.043328 0.047325 PLXDC1_E71_F 0.42 0.013035 0.01358 HCK_P858_F 0.52 0.043582 0.047507 TSC2_E140_F 0.47 0.013406 0.013938 LCN2_P86_R 0.44 0.043815 0.047609 RARRES1_P426_R 0.40 0.013514 0.014022 DES_E228_R 0.56 0.043851 0.047609 PURA_P928_R 0.51 0.014275 0.014768 TIE1_E66_R −0.42 0.044149 0.047836 MLH3_P25_F 0.29 0.01429 0.014768 PITX2_P183_R −0.42 0.044283 0.047885 TIAM1_P117_F 0.64 0.014342 0.014793 FAT_P279_R 0.44 0.044548 0.048075 MAGEL2_E166_R −0.47 0.015131 0.015575 AKT1_P310_R 0.18 0.044891 0.048349 NDN_P1110_F −0.47 0.015296 0.015714 GNG7_E310_R −0.26 0.045222 0.048609 S100A4_P887_R 0.49 0.015586 0.01598 CARD15_P665_F −0.41 0.045446 0.048753 APC_E117_R 0.34 0.015811 0.016178 GRB7_E71_R 0.43 0.045752 0.048984 MET_E333_F 0.40 0.015994 0.01632 RARB_P60_F 0.40 0.046354 0.049347 HLA-DOA_P191_R 0.38 0.016013 0.01632 CEBPA_P706_F −0.24 0.046354 0.049347 LCN2_P86_R 0.37 0.016247 0.016526 CDH11_E102_R 0.70 0.046365 0.049347 PTK6_E50_F 0.36 0.016441 0.016691 BMP3_P56_R 0.13 0.046531 0.049426 RIPK3_P24_F 0.44 0.016749 0.016962 GFI1_P45_R 0.82 0.046749 0.049561 NOS3_P38_F 0.32 0.016775 0.016962 FLT1_P615_R 0.67 0.046863 0.049584 GFI1_E136_F 0.51 0.016934 0.01709 EGF_P242_R 0.32 0.047075 0.049711 IGF2_P36_R 0.52 0.017 0.017123 ALPL_P433_F 0.38 0.047181 0.049726 CLDN4_P1120_R 0.33 0.017211 0.017302 ITGA6_P718_R 0.55 0.017366 0.017378 CD2_P68_F 0.34 0.017374 0.017378 TAL1_P817_F 0.45 0.017388 0.017378 GRB10_P260_F 0.57 0.017592 0.017548 WNT1_P79_R 0.39 0.017754 0.017659 FANCA_P1006_R −0.42 0.017797 0.017659 CD1A_P6_F −0.42 0.017807 0.017659 APOA1_P261_F 0.42 0.019333 0.019136 P2RX7_E323_R 0.37 0.019514 0.019278 LRP2_E20_F 0.43 0.019788 0.019512 NOTCH1_P1198_F 0.43 0.020345 0.020023 THPO_E483_F 0.48 0.020479 0.020116 MYB_P673_R 0.15 0.020619 0.020216 PSCA_P135_F 0.30 0.020871 0.020424 RAB32_E314_R 0.43 0.021052 0.020532 RET_P717_F 0.39 0.021075 0.020532 HDAC9_E38_F 0.44 0.021101 0.020532 GSTP1_P74_F 0.34 0.021269 0.020656 ERBB4_P255_F 0.46 0.021378 0.020723 MMP14_P208_R 0.37 0.022152 0.021433 CDH17_P376_F 0.36 0.022424 0.021645 RIPK1_P744_R 0.48 0.022455 0.021645 EDNRB_P148_R −0.39 0.023332 0.022448 KIAA0125_E29_F −0.37 0.02359 0.022654 CYP1B1_P212_F 0.34 0.023764 0.022779 PKD2_P336_R 0.24 0.023998 0.02296 LMO1_E265_R 0.40 0.02422 0.02313 HIC2_P498_F 0.53 0.024392 0.023252 TRIP6_P1274_R 0.35 0.024487 0.023299 ACTG2_E98_R 0.38 0.024735 0.023491 IL1RN_E42_F 0.31 0.025149 0.02383 EDNRB_P709_R −0.36 0.025184 0.02383 FAS_P65_F 0.30 0.025349 0.023942 SPP1_P647_F 0.30 0.025466 0.023998 FGFR2_P266_R 0.28 0.025501 0.023998 PLXDC2_P914_R 0.31 0.02571 0.024151 WRN_E57_F 0.20 0.026518 0.024864 SMARCB1_P220_R 0.30 0.026584 0.024881 TCF4_P317_F 0.40 0.026843 0.025078 PLAU_P11_F 0.39 0.027113 0.025284 TRIM29_P135_F 0.29 0.027206 0.025325 FASTK_P598_R 0.28 0.027519 0.02557 SRC_E100_R 0.30 0.027952 0.025906 EPHA7_P205_R 0.36 0.027981 0.025906 CD40_P372_R 0.42 0.028514 0.026352 BMP2_P1201_F 0.40 0.02902 0.026772 MLLT4_P1400_F 0.57 0.029128 0.026783 DDIT3_P1313_R 0.37 0.029135 0.026783 MMP10_E136_R 0.31 0.029563 0.027127 PPAT_E170_R 0.28 0.029693 0.027166 APOC2_P377_F 0.36 0.029711 0.027166 HSPA2_P162_R 0.40 0.029905 0.027271 SEMA3B_P110_R 0.33 0.02993 0.027271 H19_P1411_R −0.32 0.03002 0.027304 IL18BP_E285_F 0.36 0.030172 0.027394 KRAS_P651_F 0.21 0.030346 0.027503 CHFR_P635_R 0.37 0.0307 0.027775 MAD2L1_E93_F −0.31 0.030937 0.027941 NBL1_E205_R 0.31 0.031204 0.028133 RBL2_P250_R 0.31 0.031259 0.028133 NGFR_E328_F 0.41 0.031792 0.028563 CDH17_E31_F 0.32 0.032266 0.028938 MAPK4_E273_R −0.32 0.032516 0.029112 SRC_P297_F 0.37 0.032824 0.029337 EFNA1_P7_F 0.29 0.033925 0.030268 TRIM29_E189_F 0.31 0.034625 0.030807 MC2R_P1025_F −0.33 0.034649 0.030807 LTB4R_E64_R 0.31 0.034813 0.030901 SPARC_P195_F 0.31 0.034945 0.030964 FHIT_E19_R 0.21 0.035016 0.030974 MSH2_P1008_F 0.35 0.035525 0.031318 TNFRSF10D_P70_F 0.41 0.035527 0.031318 GFI1_P208_R 0.33 0.035754 0.031465 SKI_E465_R 0.18 0.036254 0.03185 BCL2L2_P280_F 0.36 0.036443 0.031962 TUSC3_E29_R 0.42 0.036625 0.032067 ELK3_P514_F 0.35 0.036858 0.032216 RAD50_P191_F 0.34 0.038143 0.033283 KIT_P367_R 0.40 0.038299 0.033297 LIG3_P622_R 0.28 0.038325 0.033297 CD1A_P414_R −0.52 0.038352 0.033297 HDAC1_P414_R 0.27 0.038713 0.033553 UGT1A1_P564_R 0.49 0.038802 0.033574 CPNE1_P138_F −0.42 0.039415 0.034048 PI3_E107_F −0.36 0.039628 0.034174 ITGB4_P517_F 0.28 0.040147 0.034564 CXCL9_E268_R 0.28 0.041398 0.035582 ABCG2_P178_R 0.26 0.041605 0.0357 IGFBP5_P9_R 0.40 0.043521 0.037282 DIO3_E230_R 0.38 0.043665 0.037343 EPHB3_P569_R 0.35 0.043968 0.03754 GABRA5_P862_R −0.30 0.044296 0.037718 PTPRH_P255_F 0.33 0.044322 0.037718 HSD17B12_P97_F 0.30 0.044955 0.038193 GNAS_E58_F 0.37 0.045037 0.0382 AGXT_P180_F −0.34 0.045119 0.038206 WT1_P853_F 0.41 0.045554 0.038512 CARD15_P302_R 0.40 0.046531 0.039273 AFP_P824_F −0.36 0.046897 0.039518 HGF_P1293_R −0.36 0.047957 0.040345 PRSS8_E134_R 0.25 0.048379 0.040634 MUC1_E18_R 0.26 0.048492 0.040662 ERCC3_P1210_R 0.51 0.049264 0.041243 PROM1_P44_R 0.36 0.049789 0.041615 OSM_P34_F 0.29 0.050276 0.041954 FRK_P258_F 0.30 0.051037 0.04252 ONECUT2_P315_R 0.44 0.051642 0.042954 TSP50_E21_R 0.37 0.051777 0.042997 VAMP8_P241_F 0.27 0.052199 0.043212 DIRAS3_P745_F 0.37 0.052203 0.043212 NEU1_P745_F −0.35 0.052365 0.043276 COL4A3_P545_F 0.33 0.053026 0.043753 ETS1_P559_R 0.44 0.053437 0.044022 MC2R_E455_F −0.39 0.054357 0.044708 CDC25B_E83_F 0.53 0.054498 0.044753 OGG1_E400_F 0.32 0.054712 0.044857 GATA6_P726_F 0.52 0.054832 0.044884 DDB2_P407_F −0.41 0.055252 0.045156 TUSC3_P85_R 0.33 0.05584 0.045565 ZIM3_P718_R −0.35 0.056332 0.045894 TNFRSF1B_P167_F 0.40 0.057055 0.046364 MMP14_P13_F 0.26 0.05709 0.046364 MMP3_P16_R −0.32 0.057598 0.046704 IGSF4_P454_F 0.54 0.057718 0.046727 CEACAM1_P44_R 0.27 0.057857 0.046767 HTR2A_P853_F 0.40 0.058333 0.047077 HLA-DPB1_P540_F 0.37 0.058588 0.04716 PTHLH_P15_R 0.31 0.05863 0.04716 GPX1_E46_R 0.30 0.05871 0.04716 TFPI2_E141_F 0.44 0.058926 0.04726 GSTM1_P363_F 0.46 0.060177 0.048188 PCDH1_E22_F 0.12 0.060543 0.048406 IGFBP5_E144_F 0.31 0.062064 0.049546 NNAT_P544_R 0.42 0.062614 0.049907 *Positive coefficient indicates increased methylation in invasive tumors

SUPPLEMENTAL TABLE 16 Rank order of CpGs most differentially methylated between RPMM class 4 (with significantly higher prevalence of invasive bladder tumors) and other RPMM classes. Series 1 Series 2 GENE_CpG AUC for Class 4 vs other GENE_CpG AUC for Class 4 vs other CASP10_P186_F 0.877 NPY_E31_R 0.917 THBS2_P605_R 0.865 HS3ST2_E145_R 0.917 KRT13_P341_R 0.861 NPY_P295_F 0.915 CXCL9_E268_R 0.859 MYOD1_E156_F 0.907 SMO_P455_R 0.854 SOX1_P294_F 0.894 TGFB3_E58_R 0.850 HS3ST2_P171_F 0.892 PRSS8_E134_R 0.849 SLIT2_E111_R 0.875 SERPINB5_P19_R 0.846 TMEFF2_P152_R 0.874 TJP1_P326_R 0.841 FGF2_P229_F 0.873 KRT5_P308_F 0.841 EYA4_E277_F 0.870 FGFR4_P610_F 0.838 SOX1_P1018_R 0.868 FGF1_P357_R 0.836 DLK1_E227_R 0.866 FGF1_E5_F 0.836 IRAK3_P185_F 0.863 TRIM29_P135_F 0.834 TMEFF2_E94_R 0.860 MYCN_P464_R 0.833 RBP1_E158_F 0.855 NOS3_P38_F 0.831 CDH11_P354_R 0.849 MAP3K1_P7_F 0.830 FGF3_E198_R 0.844 NBL1_E205_R 0.830 CDH11_P203_R 0.841 SLC14A1_E295_F 0.829 SLC5A8_E60_R 0.837 EFNB3_P442_R 0.828 FGF3_P171_R 0.835 RIPK1_P868_F 0.826 PYCARD_P150_F 0.834 TMPRSS4_E83_F 0.826 VIM_P811_R 0.831 FRK_P36_F 0.822 GALR1_P80_F 0.831 IRF5_P123_F 0.822 MOS_E60_R 0.827 TRIM29_E189_F 0.816 HS3ST2_P546_F 0.825 CSF2_E248_R 0.815 CDH13_P88_F 0.825 BMP4_P199_R 0.814 GALR1_E52_F 0.824 MST1R_E42_R 0.814 NTSR1_E109_F 0.823 VAMP8_P241_F 0.811 IRAK3_P13_F 0.822 ACVR1_E328_R 0.810 NPY_P91_F 0.821 NID1_P714_R 0.810 SOX17_P287_R 0.819 SPDEF_P6_R 0.809 SMO_E57_F 0.819 MMP7_E59_F 0.808 TP73_P945_F 0.818 UGT1A1_P315_R 0.808 EPHA5_E158_R 0.815 KRT5_E196_R 0.807 CDH11_E102_R 0.813 SFN_E118_F 0.807 FLT4_E206_F 0.812 CSF1R_P73_F 0.804 AGTR1_P154_F 0.811 FRK_P258_F 0.804 CSPG2_P82_R 0.808 ACVR1C_P115_R 0.803 TERT_P360_R 0.807 AOC3_P890_R 0.803 GDF10_P95_R 0.807 PCDH1_E22_F 0.803 TPEF_seq_44_S88_R 0.806 ACVR1_P983_F 0.800 ZIM2_P22_F 0.805 IRF7_E236_R 0.800 TPEF_seq_44_S36_F 0.804 TRPM5_P979_F 0.800 AGTR1_P41_F 0.803 FANCF_P13_F 0.798 KDR_P445_R 0.803 CREBBP_P712_R 0.798 FGF8_P473_F 0.803 STAT5A_P704_R 0.797 CDH13_E102_F 0.802 CSF2_P605_F 0.796 PENK_E26_F 0.799 IGF2R_P396_R 0.795 IRAK3_E130_F 0.796 IRAK3_P13_F 0.792 WNT2_P217_F 0.795 LIG3_P622_R 0.792 HTR1B_E232_R 0.794 SRC_P297_F 0.792 TAL1_P594_F 0.794 PAX6_E129_F 0.791 MDR1_seq_42_S300_R 0.794 CDH17_P376_F 0.790 RASSF1_P244_F 0.792 IRAK3_P185_F 0.790 GAS7_E148_F 0.791 MBD2_P233_F 0.790 IPF1_P750_F 0.790 CDH17_E31_F 0.789 DBC1_E204_F 0.790 SRC_P164_F 0.789 CD9_P585_R 0.789 EGF_P413_F 0.788 CFTR_P372_R 0.788 EDN1_E50_R 0.787 CFTR_P115_F 0.788 CEACAM1_P44_R 0.786 CCND2_P887_F 0.788 HLA-DOA_P191_R 0.785 HLF_E192_F 0.785 IL1RN_E42_F 0.783 NTSR1_P318_F 0.784 IRAK3_E130_F 0.781 ADCYAP1_P455_R 0.783 RARA_P176_R 0.781 DCC_P471_R 0.782 KRT13_P676_F 0.780 STAT5A_P704_R 0.781 FGF2_P229_F 0.779 CCNA1_E7_F 0.780 PI3_P274_R 0.776 DES_E228_R 0.780 GRB10_E85_R 0.775 ADAMTS12_E52_R 0.780 NOS2A_E117_R 0.774 MYOD1_P50_F 0.780 HDAC1_P414_R 0.772 RIPK1_P868_F 0.779 S100A2_P1186_F 0.772 DBC1_P351_R 0.778 LMO1_E265_R 0.771 RBP1_P150_F 0.777 CD9_P585_R 0.771 HHIP_E94_F 0.776 CHFR_P635_R 0.771 RBP1_P426_R 0.776 SNCG_P53_F 0.769 CHGA_E52_F 0.772 IL1RN_P93_R 0.767 PLXDC2_E337_F 0.772 SNCG_E119_F 0.766 VIM_P343_R 0.771 SHH_E328_F 0.765 FLI1_E29_F 0.771 MCM2_P241_R 0.765 SFRP1_E398_R 0.771 ERBB4_P541_F 0.765 TERT_E20_F 0.771 NOTCH1_P1198_F 0.763 SLIT2_P208_F 0.770 GAS7_P622_R 0.762 PENK_P447_R 0.770 LCN2_P141_R 0.761 HOXB2_P488_R 0.769 AATK_E63_R 0.761 SMO_P455_R 0.769 TGFB2_E226_R 0.760 EYA4_P794_F 0.768 DLL1_P832_F 0.759 EYA4_P508_F 0.767 PTPN6_P282_R 0.759 DIO3_P674_F 0.767 TRIM29_P261_F 0.758 NEFL_P209_R 0.766 E2F5_P516_R 0.758 KDR_E79_F 0.766 ALOX12_E85_R 0.757 CALCA_E174_R 0.765 SNCG_P98_R 0.757 FRZB_E186_R 0.765 CLDN4_P1120_R 0.757 MT1A_P600_F 0.764 SYK_E372_F 0.756 FLT3_E326_R 0.764 HOXB2_P99_F 0.755 IGF2_P1036_R 0.763 MFAP4_P197_F 0.754 CCND2_P898_R 0.763 IGFBP1_E48_R 0.754 SFRP1_P157_F 0.763 CSF1R_E26_F 0.754 RASSF1_E116_F 0.762 TMPRSS4_P552_F 0.753 SPI1_P48_F 0.762 IL2_P607_R 0.752 ISL1_P379_F 0.762 FRZB_E186_R 0.751 ADCYAP1_P398_F 0.762 MMP14_P13_F 0.751 PTPRG_P476_F 0.762 CRK_P721_F 0.751 HTR1B_P107_F 0.761 AFF3_P808_F 0.749 IGFBP2_P306_F 0.761 MMP14_P208_R 0.749 IGF2AS_P203_F 0.761 RASSF1_E116_F 0.748 HCK_P46_R 0.760 IGFBP6_E47_F 0.747 FLT4_P180_R 0.760 LCN2_P86_R 0.746 TBX1_P520_F 0.759 ALOX12_P223_R 0.745 EPHA5_P66_F 0.759 GSTM2_P453_R 0.743 HOXB2_P99_F 0.759 CD40_P372_R 0.743 KRT13_P676_F 0.759 MAS1_P657_R 0.742 FLT3_P302_F 0.759 FASTK_P598_R 0.742 GPX3_E178_F 0.758 MMP3_P16_R 0.742 KIT_P405_F 0.757 P2RX7_P597_F 0.742 ST6GAL1_P528_F 0.756 PTPRH_E173_F 0.741 DIO3_E230_R 0.754 VAV1_P317_F 0.741 CD9_P504_F 0.754 SFTPA1_E340_R 0.741 CALCA_P75_F 0.754 EPHX1_P22_F 0.740 TGFB2_E226_R 0.753 GABRA5_E44_R 0.739 COL18A1_P494_R 0.752 KCNK4_P171_R 0.739 CYP1B1_E83_R 0.752 XRCC2_P1077_F 0.739 HTR1B_P222_F 0.751 ABCG2_P178_R 0.738 PTPRG_E40_R 0.750 GSTM2_E153_F 0.738 TSP50_E21_R 0.749 ACVR1C_P363_F 0.738 FLT1_P615_R 0.749 AIM2_E208_F 0.737 OAT_P465_F 0.749 NTSR1_P318_F 0.737 ISL1_E87_R 0.747 S100A2_E36_R 0.737 TWIST1_P44_R 0.747 IGF2AS_P203_F 0.737 COL1A2_E299_F 0.746 PSCA_P135_F 0.737 ASCL2_P360_F 0.746 MEG3_E91_F 0.737 MT1A_E13_R 0.745 PPARG_P693_F 0.736 ASCL1_E24_F 0.745 TNFRSF1A_P678_F 0.736 NTRK3_P752_F 0.744 TRIP6_P1090_F 0.736 GABRB3_E42_F 0.744 MUC1_E18_R 0.736 NRG1_E74_F 0.744 MYB_P673_R 0.735 KRT13_P341_R 0.743 EMR3_P39_R 0.735 FLI1_P620_R 0.743 SHB_P691_R 0.735 PROK2_P390_F 0.741 TNFRSF10A_P91_F 0.734 ASCL2_E76_R 0.741 SLIT2_P208_F 0.734 GAS7_P622_R 0.740 SRC_E100_R 0.734 ZIM2_E110_F 0.740 JAG2_P264_F 0.734 ERG_E28_F 0.740 RIPK4_E166_F 0.733 FRZB_P406_F 0.739 MLH3_P25_F 0.733 OPCML_E219_R 0.739 SLC14A1_P369_R 0.733 GP1BB_P278_R 0.739 IGF1R_P325_R 0.733 ADAMTS12_P250_R 0.739 CCL3_E53_R 0.733 TAL1_E122_F 0.738 MMP19_E274_R 0.733 RAN_P581_R 0.738 UGT1A1_E11_F 0.733 IFNGR2_E164_F 0.737 JUNB_P1149_R 0.733 IGFBP7_P297_F 0.737 CASP8_E474_F 0.731 BDNF_E19_R 0.735 SPI1_P929_F 0.731 NGFR_P355_F 0.734 IGFBP6_P328_R 0.731 GSTM2_P109_R 0.734 FGFR1_E317_F 0.730 PODXL_P1341_R 0.734 JAK3_P1075_R 0.730 GSTM2_P453_R 0.734 SYK_P584_F 0.729 TAL1_P817_F 0.734 PDGFRB_P273_F 0.729 IGF2AS_E4_F 0.733 ER_seq_a1_S60_F 0.729 POMC_P400_R 0.732 GLI2_P295_F 0.728 AATK_P519_R 0.732 TFF2_P178_F 0.728 PALM2-AKAP2_P420_R 0.731 GABRG3_P75_F 0.727 MLLT4_P1400_F 0.730 MMP9_P189_F 0.726 ISL1_P554_F 0.730 MST1R_P87_R 0.726 KIT_P367_R 0.730 FGF6_E294_F 0.726 MYH11_P236_R 0.729 ZNFN1A1_P179_F 0.726 NTRK3_E131_F 0.729 GJB2_P931_R 0.726 HIC2_P498_F 0.729 PWCR1_E81_R 0.725 TIMP3_seq_7_S38_F 0.729 CPA4_E20_F 0.725 WT1_E32_F 0.728 NPY_P295_F 0.725 CCKBR_P480_F 0.727 NID1_P677_F 0.724 ETV1_P235_F 0.727 MMP3_P55_F 0.723 RET_seq_54_S260_F 0.726 CDK10_P199_R 0.723 KRT5_P308_F 0.726 DDR2_P743_R 0.722 GUCY2D_E419_R 0.725 CARD15_P302_R 0.722 HLA-F_E402_F 0.725 ATP10A_P147_F 0.722 HLA-DOA_P191_R 0.724 NOS2A_P288_R 0.721 THY1_P149_R 0.724 FES_P223_R 0.721 MMP2_P197_F 0.724 CEACAM1_E57_R 0.721 ALOX12_P223_R 0.723 DNMT3B_P352_R 0.721 RASGRF1_E16_F 0.723 PTK2B_P673_R 0.721 PRKCDBP_E206_F 0.723 CD9_P504_F 0.721 MYH11_P22_F 0.722 ZAP70_P220_R 0.721 ALPL_P278_F 0.722 MAPK14_P327_R 0.720 DCC_E53_R 0.722 TERT_P360_R 0.719 EPO_E244_R 0.722 TRIP6_P1274_R 0.718 RIPK3_P124_F 0.721 MAF_P826_R 0.718 CALCA_P171_F 0.721 TGFA_P642_R 0.718 HPN_P823_F 0.721 SFTPC_E13_F 0.718 POMC_P53_F 0.721 ID1_P659_R 0.717 FGFR1_P204_F 0.720 WNT8B_P216_R 0.716 THY1_P20_R 0.720 HBII-52_P563_F 0.716 FGF1_P357_R 0.719 TFF1_P180_R 0.716 GSTM2_E153_F 0.718 P2RX7_E323_R 0.716 GJB2_P931_R 0.717 SNRPN_P230_R 0.716 CD40_E58_R 0.717 TEK_E75_F 0.716 CSPG2_E38_F 0.717 PLAT_P80_F 0.715 PYCARD_P393_F 0.716 RIPK3_P124_F 0.715 GJB2_P791_R 0.716 DHCR24_P406_R 0.715 GSTP1_P74_F 0.716 NPY_E31_R 0.714 ACVR1_E328_R 0.715 ESR1_E298_R 0.713 TBX1_P885_R 0.715 IL12A_E287_R 0.713 SLC5A8_P38_R 0.715 ENC1_P484_R 0.713 F2R_P839_F 0.713 TSC2_E140_F 0.712 ALPL_P433_F 0.713 IL1B_P582_R 0.712 CD44_E26_F 0.713 ITGB4_E144_F 0.712 KRT5_E196_R 0.713 FAS_P322_R 0.711 TFPI2_P9_F 0.713 RAD50_P191_F 0.710 HPN_P374_R 0.713 RARRES1_E235_F 0.710 VAV1_P317_F 0.713 TMEFF1_P626_R 0.709 PDGFB_P719_F 0.713 TNK1_P41_R 0.708 SOX17_P303_F 0.712 GSTM2_P109_R 0.708 IGFBP2_P353_R 0.711 TYRO3_P501_F 0.708 AATK_P709_R 0.710 BAX_E281_R 0.707 IL18BP_P51_R 0.710 IL3_P556_F 0.707 IGF2_P36_R 0.710 HOXB2_P488_R 0.707 TNFRSF10C_P7_F 0.710 BCL2L2_P280_F 0.707 JAK3_E64_F 0.709 PADI4_E24_F 0.706 HHIP_P307_R 0.709 CAPG_E228_F 0.706 GSTM1_P363_F 0.709 SPI1_P48_F 0.706 ACVR1_P983_F 0.709 VAMP8_P114_F 0.705 PDGFRB_P273_F 0.709 HCK_P858_F 0.705 RIPK1_P744_R 0.709 FGFR2_P266_R 0.705 ITGA6_P718_R 0.708 GPR116_E328_R 0.705 DIO3_P90_F 0.708 SEMA3B_P110_R 0.703 NRG1_P558_R 0.708 SFN_P248_F 0.702 NGFR_E328_F 0.708 NEFL_P209_R 0.701 MFAP4_P197_F 0.708 VAMP8_E7_F 0.701 COL1A1_P5_F 0.708 RARRES1_P426_R 0.701 MMP2_E21_R 0.708 NR2F6_E375_R 0.700 COL1A2_P48_R 0.707 EMR3_E61_F 0.700 RET_seq_53_S374_F 0.707 B3GALT5_P330_F 0.700 NTRK2_P10_F 0.706 PTPRO_E56_F 0.700 CCNA1_P216_F 0.706 ITK_E166_R 0.700 FZD9_P175_F 0.706 EVI1_E47_R 0.700 PDGFRB_P343_F 0.705 BCL6_P248_R 0.699 ST6GAL1_P164_R 0.704 MDS1_E45_F 0.699 SEZ6L_P249_F 0.704 MC2R_P1025_F 0.699 NPR2_P618_F 0.703 MCC_P196_R 0.699 GFI1_P45_R 0.703 BLK_P668_R 0.698 GSTP1_E322_R 0.703 CSF1_P339_F 0.698 PDGFRA_P1429_F 0.702 DAPK1_E46_R 0.698 VAV1_E9_F 0.702 LY6G6E_P45_R 0.698 ALK_E183_R 0.702 MPL_P657_F 0.697 F2R_P88_F 0.701 HLA-DQA2_E93_F 0.697 SLC22A3_P528_F 0.701 CA5P10_P334_F 0.697 EPHA7_E6_F 0.701 ETV6_E430_F 0.696 MEG3_P235_F 0.700 PTPN6_E171_R 0.696 DLL1_P832_F 0.699 ERG_E28_F 0.696 NTRK3_P636_R 0.699 HLA-DPA1_P205_R 0.696 TEK_E75_F 0.699 DLC1_E276_F 0.695 HIC-1_seq_48_S103_R 0.698 IGF1R_E186_R 0.695 SPARC_E50_R 0.698 CD1A_P414_R 0.695 IL1B_P582_R 0.698 EPHB3_E0_F 0.694 IGSF4_P86_R 0.698 DDR1_P332_R 0.694 NOTCH4_E4_F 0.698 PDGFB_P719_F 0.694 CD40_P372_R 0.697 CSF3_P309_R 0.694 LEFTY2_P719_F 0.697 HRASLS_P353_R 0.694 GRB10_P496_R 0.697 LRP2_E20_F 0.693 PALM2-AKAP2_P183_R 0.697 HOXA9_P1141_R 0.693 TWIST1_E117_R 0.697 MYLK_P469_R 0.693 CYP1B1_P212_F 0.697 CYP1A1_P382_F 0.693 KLK10_P268_R 0.697 GP1BB_P278_R 0.693 ASCL1_P747_F 0.696 ERBB4_P255_F 0.693 FABP3_P598_F 0.696 ITPR3_P1112_F 0.692 MPL_P62_F 0.696 RHOH_P121_F 0.692 TMEFF2_P210_R 0.696 HS3ST2_E145_R 0.692 HIC2_P528_R 0.696 TBX1_P520_F 0.692 GDF10_E39_F 0.695 RET_P717_F 0.692 LMO1_E265_R 0.695 IRF7_P277_R 0.691 CSF3_P309_R 0.695 NDN_E131_R 0.691 JAK3_P156_R 0.694 EPHA1_E46_R 0.691 SCGB3A1_E55_R 0.693 INHA_P1144_R 0.691 IL18BP_E285_F 0.693 RASSF1_P244_F 0.691 DIRAS3_P745_F 0.693 TFF2_P557_R 0.690 SLC5A5_E60_F 0.693 HOXA5_P479_F 0.690 PCDH1_E22_F 0.693 ZIM3_E203_F 0.690 NTRK2_P395_R 0.692 GRB7_P160_R 0.690 PDGFRA_E125_F 0.692 OAT_P465_F 0.689 TNFRSF10C_E109_F 0.692 DAPK1_P10_F 0.689 DIRAS3_E55_R 0.692 PADI4_P1158_R 0.689 PRDM2_P1340_R 0.692 IPF1_P750_F 0.689 CSF1R_E26_F 0.692 TGFBI_P31_R 0.689 RET_P717_F 0.692 GRB10_P260_F 0.688 COL18A1_P365_R 0.691 RIPK3_P24_F 0.688 ALOX12_E85_R 0.691 PTCH2_E173_F 0.688 TJP2_P518_F 0.691 HLA-DOB_E432_R 0.687 FLT1_E444_F 0.691 BCR_P346_F 0.687 EGF_P242_R 0.691 PLA2G2A_P528_F 0.687 EPHA7_P205_R 0.691 MCAM_P169_R 0.687 TSP50_P137_F 0.691 EPHA2_P203_F 0.686 IL17RB_E164_R 0.690 TYRO3_P366_F 0.686 TCF4_P317_F 0.689 CLK1_P538_F 0.686 FGF1_E5_F 0.689 FHIT_E19_R 0.685 FGF8_E183_F 0.688 HFE_E273_R 0.685 PDE1B_E141_F 0.688 ABCB4_P51_F 0.684 NGFB_P13_F 0.688 SMARCB1_P220_R 0.684 EGF_P413_F 0.687 MMP10_E136_R 0.684 LRRC32_P865_R 0.687 CDKN1A_P242_F 0.684 ACTG2_E98_R 0.686 VIM_P811_R 0.683 CSF3R_P8_F 0.685 CTNNA1_P382_R 0.683 TRPM5_P979_F 0.684 DUSP4_E61_F 0.683 SOD3_P225_F 0.684 GRB7_E71_R 0.683 ZNF215_P71_R 0.684 IGFBP2_P353_R 0.682 ETV1_P515_F 0.684 IAPP_E280_F 0.682 ABO_E110_F 0.684 DSC2_E90_F 0.682 EPO_P162_R 0.684 TCF7L2_E411_F 0.681 TNF_P1084_F 0.683 SPP1_P647_F 0.681 APOA1_P75_F 0.683 LIF_E208_F 0.681 DSC2_P407_R 0.683 PTPRH_P255_F 0.681 NGFB_E353_F 0.683 MYCN_E77_R 0.680 PTCH2_P37_F 0.683 SPP1_E140_R 0.680 MFAP4_P10_R 0.683 APOA1_P261_F 0.680 S100A4_P194_R 0.683 CDH13_P88_F 0.680 FGFR1_E317_F 0.683 LRRK1_P39_F 0.680 MEG3_E91_F 0.682 USP29_P282_R 0.679 SLC22A3_P634_F 0.682 GPX3_E178_F 0.679 FLT1_P302_F 0.681 TNFRSF10C_E109_F 0.679 IGSF4_P454_F 0.681 GNAS_P86_F 0.679 GLI3_P453_R 0.681 FES_E34_R 0.678 STAT5A_E42_F 0.680 MMP1_P460_F 0.678 LMO2_P794_R 0.680 p16_seq_47_S188_R 0.678 GSTM1_P266_F 0.680 TFDP1_P543_R 0.677 MMP19_E274_R 0.679 CPA4_P961_R 0.677 DSG1_E292_F 0.679 ZP3_P220_F 0.677 DNAJC15_E26_R 0.679 HIC1_P565_R 0.677 FGF5_E16_F 0.679 ITGA6_P718_R 0.677 TJP2_P330_R 0.679 SEMA3F_E333_R 0.676 MATK_P190_R 0.679 MMP8_E89_R 0.676 HOXA5_P1324_F 0.678 EGFR_P260_R 0.676 CSF2_P605_F 0.678 TNFRSF10C_P7_F 0.675 GABRB3_P92_F 0.678 P2RX7_P119_R 0.675 LRRC32_E157_F 0.678 TDG_E129_F 0.675 WNT10B_P993_F 0.677 PYCARD_E87_F 0.674 BDNF_P259_R 0.677 GALR1_E52_F 0.674 MST1R_P392_F 0.676 PTCH_E42_F 0.674 KCNK4_P171_R 0.676 TMEFF2_P152_R 0.674 LRRK1_P39_F 0.676 HBII-52_P659_F 0.674 EPHA3_P106_R 0.675 SLC22A2_E271_R 0.673 HOXA5_P479_F 0.674 RARA_E128_R 0.673 RARB_E114_F 0.674 FAS_P65_F 0.673 PLA2G2A_E268_F 0.674 PYCARD_P150_F 0.672 CTNNB1_P757_F 0.674 DLC1_P88_R 0.672 PLG_E406_F 0.674 F2R_P88_F 0.672 HCK_P858_F 0.673 MOS_E60_R 0.672 WT1_P853_F 0.672 MAPK10_E26_F 0.671 GP1BB_E23_F 0.672 PLAT_E158_F 0.671 THBS2_P605_R 0.672 RIPK4_P172_F 0.671 GFI1_E136_F 0.671 TGFB1_P833_R 0.670 SHH_P104_R 0.671 PPAT_E170_R 0.670 EVI2A_P94_R 0.671 NBL1_P24_F 0.670 FGF7_P610_F 0.671 HLA-DPB1_P540_F 0.669 DCC_P177_F 0.670 CD44_E26_F 0.669 PDE1B_P263_R 0.670 GLI2_E90_F 0.669 IGFBP7_P371_F 0.670 IGFBP5_P9_R 0.668 DDR2_P743_R 0.669 EPHX1_E152_F 0.668 MSH2_P1008_F 0.669 PXN_P308_F 0.668 PTHR1_E36_R 0.669 ATP10A_P524_R 0.668 MCAM_P265_R 0.669 IGFBP3_E65_R 0.667 DDR2_E331_F 0.668 CTGF_E156_F 0.667 SERPINE1_E189_R 0.668 CDK10_E74_F 0.667 ERN1_P809_R 0.667 GAS1_P754_R 0.667 ABO_P312_F 0.667 TGFBR3_P429_F 0.667 COMT_E401_F 0.667 LIMK1_P709_R 0.666 BMP6_P163_F 0.667 TMEFF1_P234_F 0.666 MMP2_P303_R 0.667 TJP1_P390_F 0.666 CHD2_P667_F 0.666 BLK_P14_F 0.666 SEZ6L_P299_F 0.666 ABCC2_E16_R 0.666 TWIST1_P355_R 0.665 APBA1_E99_R 0.666 WNT1_P79_R 0.665 NKX3-1_P871_R 0.665 EVI2A_E420_F 0.664 CSPG2_P82_R 0.665 IL1A_E113_R 0.664 THPO_E483_F 0.665 HOXA5_E187_F 0.664 SMO_E57_F 0.665 XPC_P226_R 0.664 MUSK_P308_F 0.664 FES_P223_R 0.664 TMEFF2_P210_R 0.664 TGFB2_P632_F 0.664 STAT5A_E42_F 0.664 TNFRSF1A_P678_F 0.663 IL6_E168_F 0.664 SEMA3C_P642_F 0.662 TJP2_P330_R 0.663 FOLR1_E368_R 0.662 TNFSF10_P2_R 0.663 FES_E34_R 0.662 CTSD_P726_F 0.663 NPR2_P1093_F 0.662 EDN1_P39_R 0.662 IL10_P85_F 0.661 GATA6_P21_R 0.661 FZD9_E458_F 0.661 DST_E31_F 0.661 MLF1_E243_F 0.661 EYA4_E277_F 0.661 CSF2_E248_R 0.661 HSD17B12_P97_F 0.660 CDC25B_P11_R 0.661 PLAUR_E123_F 0.660 TIE1_E66_R 0.661 TERT_E20_F 0.660 S100A4_P887_R 0.660 SPI1_E205_F 0.659 TGFB1_P833_R 0.660 PGF_E33_F 0.659 CCKBR_P361_R 0.660 IGF2AS_E4_F 0.659 EPHX1_P22_F 0.659 ZIM3_P718_R 0.659 MME_E29_F 0.659 NPR2_P1093_F 0.659 S100A4_E315_F 0.659 RUNX3_P247_F 0.659 TFPI2_P152_R 0.658 PSCA_E359_F 0.659 SOD3_P460_R 0.658 GRB10_P496_R 0.659 GRB10_P260_F 0.658 HBII-52_E142_F 0.658 RAB32_E314_R 0.657 CPNE1_P138_F 0.658 TCF4_P175_R 0.657 MMP19_P306_F 0.658 TNFRSF10D_P70_F 0.657 HS3ST2_P171_F 0.658 HDAC9_E38_F 0.656 ERCC6_P698_R 0.658 MME_P388_F 0.655 RARA_P1076_R 0.658 CDC25B_E83_F 0.655 SEPT9_P58_R 0.657 CD44_P87_F 0.654 GPX1_P194_F 0.657 FHIT_E19_R 0.654 SERPINE1_P519_F 0.657 ETS1_P559_R 0.654 IGF1_E394_F 0.657 ALK_P28_F 0.654 GLI3_P453_R 0.656 HLA-DOA_P594_F 0.654 ITK_P114_F 0.656 ZNF264_P397_F 0.653 EPHA1_P119_R 0.656 P2RX7_P119_R 0.653 BCR_P422_F 0.656 PLXDC1_P236_F 0.653 DSP_P36_F 0.656 ACTG2_P346_F 0.653 TUSC3_E29_R 0.656 CSF1_P339_F 0.653 IGFBP1_P12_R 0.655 LTB4R_E64_R 0.653 SH3BP2_E18_F 0.655 PTHLH_E251_F 0.653 PITX2_P183_R 0.655 COL4A3_E205_R 0.653 BRCA1_P835_R 0.655 PLAGL1_P236_R 0.652 OGG1_E400_F 0.655 FGF7_P44_F 0.652 PKD2_P287_R 0.655 ASCL2_P609_R 0.652 CD44_P87_F 0.654 LRP2_E20_F 0.652 HPN_P823_F 0.654 JAK3_P1075_R 0.652 PWCR1_P811_F 0.653 TMEFF1_P626_R 0.652 KCNQ1_P546_R 0.653 UGT1A1_P564_R 0.651 EPHA2_P340_R 0.653 RUNX3_P393_R 0.651 PLG_P370_F 0.653 SPP1_E140_R 0.651 HOXA9_E252_R 0.652 CD86_P3_F 0.651 EGF_P242_R 0.652 NID1_P714_R 0.650 KLK10_P268_R 0.652 HOXC6_P585_R 0.650 RUNX3_E27_R 0.652 TMPRSS4_P552_F 0.650 CCNA1_E7_F 0.652 RARA_P176_R 0.650 MST1R_P392_F 0.651 HBII-52_P659_F 0.650 DCN_P1320_R 0.651 MYBL2_P211_F 0.649 CYP1B1_E83_R 0.651 OPCML_P71_F 0.649 NEO1_P1067_F 0.651 PTPNS1_P301_R 0.649 HLA-DRA_P132_R 0.650 EPHA3_E156_R 0.649 PTK6_E50_F 0.650 GSTP1_seq_38_S153_R 0.648 VIM_P343_R 0.650 TIAM1_P188_R 0.648 RIPK1_P744_R 0.649 ERCC3_P1210_R 0.648 CCND1_E280_R 0.649 BLK_P14_F 0.648 SPDEF_E116_R 0.649 TFPI2_E141_F 0.648 PHLDA2_P622_F 0.649 SLC14A1_P369_R 0.647 NEU1_P745_F 0.649 INS_P804_R 0.647 SLC22A3_P528_F 0.649 ATP10A_P147_F 0.647 PTPRF_E178_R 0.649 TNFRSF10D_E27_F 0.647 USP29_E274_F 0.648 PPAT_E170_R 0.647 TGFBR3_E188_R 0.648 TRIM29_P261_F 0.646 EXT1_E197_F 0.647 DST_E31_F 0.646 MFAP4_P10_R 0.647 CDKN1C_P626_F 0.646 HLA-DPA1_P28_R 0.647 MST1R_P87_R 0.646 IL1A_E113_R 0.647 MT1A_P49_R 0.646 TNFSF8_E258_R 0.647 HRASLS_P353_R 0.646 ITGA2_E120_F 0.646 SLC22A3_E122_R 0.645 HPSE_P93_F 0.646 TNFRSF1B_E5_F 0.645 AATK_P519_R 0.646 SLC14A1_E295_F 0.645 PI3_P1394_R 0.646 TDGF1_E53_R 0.645 EPHB2_P165_R 0.646 IGFBP5_P9_R 0.645 CD82_P557_R 0.645 THPO_E483_F 0.644 DAB2IP_E18_R 0.645 PTCH_E42_F 0.644 HIF1A_P488_F 0.645 SYK_P584_F 0.644 HLA-DPA1_E35_R 0.645 EPHX1_E152_F 0.643 MKRN3_P108_F 0.645 GATA6_P21_R 0.643 H19_P541_F 0.644 APOA1_P261_F 0.643 BMP2_E48_R 0.644 LTA_P214_R 0.643 DKFZP564O0823_E4 0.644 CTGF_E156_F 0.642 APBA2_P305_R 0.644 RARA_P1076_R 0.642 PTHR1_P258_F 0.643 MLH1_P381_F 0.642 PDGFRA_P1429_F 0.643 IFNGR2_P377_R 0.641 XRCC1_P681_R 0.643 MMP7_P613_F 0.641 ACVR1B_P572_R 0.643 TFAP2C_P765_F 0.641 COL1A1_P5_F 0.643 GPR116_E328_R 0.641 MGMT_P281_F 0.643 HLA-DOB_E432_R 0.641 ASCL2_P609_R 0.642 DAB2IP_E18_R 0.641 LYN_E353_F 0.642 SEPT9_P374_F 0.641 HOXA5_P1324_F 0.642 PTHR1_P170_R 0.641 ABCC5_P444_F 0.642 SHH_E328_F 0.640 CCND1_P343_R 0.642 TIAM1_P117_F 0.640 HPN_P374_R 0.641 HSD17B12_E145_R 0.640 PAX6_P1121_F 0.641 LTB4R_P163_F 0.639 UGT1A7_P751_R 0.641 EPHB6_E342_F 0.639 KLF5_E190_R 0.641 TNC_P57_F 0.639 PARP1_P610_R 0.641 GRB10_E85_R 0.639 CHGA_P243_F 0.640 CD2_P68_F 0.639 NFKB1_P336_R 0.640 PAX6_P1121_F 0.639 SLC22A18_P472_R 0.640 TUSC3_E29_R 0.638 DSG1_P159_R 0.640 GPR116_P850_F 0.638 HOXA5_E187_F 0.639 IL6_P213_R 0.638 GPX1_E46_R 0.639 PLXDC2_P914_R 0.637 MAP2K6_P297_R 0.639 MLH3_P25_F 0.637 MC2R_E455_F 0.639 TIMP2_P267_F 0.637 IRF5_E101_F 0.639 RAD50_P191_F 0.637 RAD54B_P227_F 0.639 GML_E144_F 0.636 COL1A2_E299_F 0.639 PDGFA_P841_R 0.636 NKX3-1_P146_F 0.638 SGCE_P250_R 0.636 SEMA3A_P658_R 0.638 FGFR4_P610_F 0.636 KRAS_P651_F 0.638 BMP2_P1201_F 0.636 HBII-13_P991_R 0.638 IL10_P348_F 0.636 DST_P262_R 0.638 WNT10B_P823_R 0.636 ASB4_P52_R 0.638 BMP3_E147_F 0.635 CD34_P339_R 0.638 ABCB4_P51_F 0.635 AGXT_E115_R 0.637 ACTG2_P455_R 0.635 CCNC_P132_R 0.637 RAP1A_P285_R 0.635 TCF4_P317_F 0.637 SEMA3A_P658_R 0.635 ZMYND10_P329_F 0.637 MMP19_P306_F 0.634 CAV1_P169_F 0.637 MAS1_P657_R 0.634 GNMT_E126_F 0.637 SFTPB_P689_R 0.634 EPS8_P437_F 0.637 HLA-DPB1_P450_F 0.634 CDH13_E102_F 0.636 LOX_P313_R 0.633 CALCA_P171_F 0.636 KRAS_E82_F 0.633 ZIM3_P451_R 0.636 NOTCH3_E403_F 0.633 CDKN1C_P6_R 0.636 POMC_E254_F 0.633 BMP6_P398_F 0.635 SFTPA1_E340_R 0.633 GATA6_P726_F 0.635 AKT1_P310_R 0.633 TFPI2_P152_R 0.635 BMPR1A_E88_F 0.632 SNRPN_seq_18_S99_F 0.635 COL4A3_P545_F 0.632 ZMYND10_E77_R 0.634 CSF1R_P73_F 0.632 BMPR1A_P956_F 0.634 BMP4_P199_R 0.631 BMP2_P1201_F 0.634 CHFR_P635_R 0.631 ICA1_P72_R 0.634 GUCY2D_P48_R 0.631 DIO3_E230_R 0.633 ERBB4_P541_F 0.631 MAP3K8_P1036_F 0.633 HSD17B12_P97_F 0.631 TNFRSF10D_E27_F 0.633 CD34_E20_R 0.631 TAL1_P594_F 0.633 MMP9_P189_F 0.630 NPR2_P618_F 0.633 PMP22_P1254_F 0.630 CD34_P780_R 0.633 TNFRSF10C_P612_R 0.630 IFNGR1_P307_F 0.632 TP73_P496_F 0.630 WNT2B_P1195_F 0.632 SLC22A18_P472_R 0.629 TP73_P945_F 0.632 THBS1_E207_R 0.629 GNMT_P197_F 0.632 MSH3_P13_R 0.629 TGFB2_P632_F 0.631 AATK_E63_R 0.629 ASB4_E89_F 0.631 MST1R_E42_R 0.629 MMP1_P397_R 0.631 EPHA8_P456_R 0.629 CYP2E1_E53_R 0.631 TP73_E155_F 0.629 CD2_P68_F 0.630 ROR2_E112_F 0.629 DBC1_E204_F 0.630 RHOH_P121_F 0.628 CSF3R_P8_F 0.630 COL1A1_P117_R 0.628 MEST_E150_F 0.630 ZAP70_P220_R 0.628 ETS2_P684_F 0.629 CEBPA_P1163_R 0.628 HLA-DQA2_P282_R 0.629 UGT1A7_P751_R 0.628 SKI_E465_R 0.629 NFKB1_P496_F 0.628 CDH11_P354_R 0.629 FZD9_P15_R 0.627 SMAD2_P848_R 0.629 PURA_P928_R 0.627 ERBB3_E331_F 0.629 DMP1_E194_F 0.627 COL4A3_P545_F 0.629 EPHB1_P503_F 0.627 PLXDC1_P236_F 0.628 FHIT_P93_R 0.627 PTGS2_P524_R 0.628 PI3_E107_F 0.627 NOTCH3_P198_R 0.628 PLXDC1_E71_F 0.627 TDGF1_P428_R 0.628 GFI1_P208_R 0.627 IFNG_E293_F 0.628 FASTK_P598_R 0.627 IL10_P348_F 0.628 HLA-DOB_P357_R 0.627 BMPR2_E435_F 0.628 NAT2_P11_F 0.626 RAN_P581_R 0.628 ESR1_E298_R 0.626 NEFL_E23_R 0.627 EPHA8_P256_F 0.625 MAPK9_P1175_F 0.627 PADI4_E24_F 0.625 MT1A_P600_F 0.627 THPO_P585_R 0.625 TNFRSF10A_P171_F 0.627 SGCE_E149_F 0.625 INHA_P1189_F 0.626 CLK1_P538_F 0.625 USP29_P205_R 0.626 IFNG_P459_R 0.625 PYCARD_P393_F 0.626 WNT1_E157_F 0.625 FAT_P973_R 0.626 IRF5_E101_F 0.624 HLA-F_E402_F 0.626 S100A2_E36_R 0.624 FHIT_P93_R 0.626 PTGS1_E80_F 0.624 SNURF_P2_R 0.625 DNMT2_P199_F 0.624 IGFBP7_P297_F 0.625 CSF3_E242_R 0.624 TK1_P62_R 0.625 BCR_P346_F 0.623 PTGS1_E80_F 0.625 PLA2G2A_P528_F 0.623 HLF_E192_F 0.625 EPS8_P437_F 0.623 MAP3K9_E17_R 0.625 BSG_P211_R 0.622 ARHGDIB_P148_R 0.625 NOS2A_P288_R 0.622 HIC1_E151_F 0.625 GNG7_P903_F 0.622 PTPNS1_E433_R 0.625 P2RX7_P597_F 0.622 COL1A2_P48_R 0.625 IMPACT_P234_R 0.622 MEST_P62_R 0.624 RASGRF1_P768_F 0.622 CSK_P740_R 0.624 CCL3_P543_R 0.622 RHOH_P953_R 0.624 PTHLH_P757_F 0.621 NCL_P1102_F 0.623 RIPK3_P24_F 0.621 GABRG3_E123_R 0.623 ELK3_P514_F 0.621 KIAA1804_P689_R 0.623 GNG7_E310_R 0.621 CD34_E20_R 0.623 MYB_P673_R 0.621 HSPA2_P162_R 0.623 RUNX3_P247_F 0.620 MET_E333_F 0.621 ITGB4_E144_F 0.620 BCAM_P205_F 0.621 PDGFRB_E195_R 0.620 THBS1_E207_R 0.621 PTGS2_P524_R 0.620 SFTPD_E169_F 0.621 TNFSF8_P184_F 0.620 HLA-DOB_P357_R 0.621 THBS2_E129_F 0.620 AXL_P223_R 0.621 USP29_P282_R 0.620 RUNX1T1_E145_R 0.620 MAPK10_E26_F 0.619 ZNF215_P71_R 0.620 NKX3-1_P871_R 0.619 JAG2_E54_F 0.620 ZIM3_P451_R 0.618 SOX17_P303_F 0.620 SNURF_P2_R 0.618 MLH1_P381_F 0.620 MPL_P657_F 0.618 HOXC6_P456_R 0.619 APC_E117_R 0.618 GP1BB_E23_F 0.619 APC_P14_F 0.618 PKD2_P336_R 0.619 ER_seq_a1_S60_F 0.618 MYOD1_E156_F 0.619 PLAT_E158_F 0.618 LOX_P313_R 0.619 SPARC_P195_F 0.617 NTSR1_E109_F 0.618 EPHX1_P1358_R 0.617 CTNNA1_P185_R 0.618 CDKN1A_E101_F 0.617 ROR2_P317_R 0.618 DAPK1_P345_R 0.617 KCNK4_E3_F 0.618 PMP22_P975_F 0.617 WNT5A_E43_F 0.618 FABP3_E113_F 0.617 TSG101_P257_R 0.618 DAB2IP_P9_F 0.617 GFI1_P45_R 0.618 APBA2_P305_R 0.617 NCL_P840_R 0.618 PPARD_P846_F 0.616 AKT1_P310_R 0.618 SPI1_E205_F 0.616 FGFR3_E297_R 0.618 TUBB3_P721_R 0.616 NOTCH2_P312_R 0.617 PYCARD_E87_F 0.616 LMO2_E148_F 0.617 FAS_P322_R 0.616 PROM1_P44_R 0.617 SMARCA3_P109_R 0.615 TRPM5_P721_F 0.617 BCAM_E100_R 0.615 APC_E117_R 0.617 HSPA2_P162_R 0.615 GNAS_E58_F 0.616 PTCH2_P568_R 0.615 NOTCH4_P938_F 0.616 MC2R_E455_F 0.615 TSP50_E21_R 0.616 SNCG_P98_R 0.614 PGF_P320_F 0.616 TFF2_P557_R 0.614 MCC_E23_R 0.616 B3GALT5_P330_F 0.614 TJP2_P518_F 0.616 UGT1A1_E11_F 0.614 BSG_P211_R 0.616 ARHGAP9_P518_R 0.614 TNF_P1084_F 0.615 WNT8B_P216_R 0.614 PTEN_P438_F 0.615 AOC3_P890_R 0.613 MYH11_P236_R 0.615 HHIP_P578_R 0.613 DAB2_P468_F 0.615 ABCA1_E120_R 0.613 SIN3B_P607_F 0.615 PLAGL1_E68_R 0.613 ITPR2_P804_F 0.615 ABCB4_P892_F 0.613 ICA1_P61_F 0.615 PTPRO_P371_F 0.613 TGFBI_P173_F 0.615 FN1_E469_F 0.613 PLA2G2A_E268_F 0.615 PAX6_E129_F 0.613 MT1A_P49_R 0.615 EGF_E339_F 0.612 RASGRF1_P768_F 0.615 OSM_P34_F 0.612 E2F3_P840_R 0.614 GATA6_P726_F 0.612 NQO1_P345_R 0.614 HDAC9_P137_R 0.612 MLH3_E72_F 0.614 MAPK12_E165_R 0.612 TUBB3_P364_F 0.614 IGF2_E134_R 0.612 GDF10_E39_F 0.614 BMP4_P123_R 0.611 TNFRSF10D_P70_F 0.614 IL3_P556_F 0.611 HDAC5_E298_F 0.614 NCL_P1102_F 0.611 MEST_P4_F 0.614 CD34_P339_R 0.611 LEF7Y2_P719_F 0.614 CCNC_P132_R 0.611 SFTPB_P689_R 0.613 LY6G6E_P45_R 0.611 TUBB3_E91_F 0.613 OSM_P188_F 0.611 FER_P581_F 0.613 TMPRSS4_E83_F 0.611 DHCR24_P652_R 0.613 SLC22A18_P216_R 0.611 ABCB4_P892_F 0.612 IGSF4C_P533_R 0.611 PTK2_P735_R 0.612 TFDP1_P543_R 0.610 LTB4R_P163_F 0.612 MOS_P27_R 0.610 GSTP1_P74_F 0.612 EPHB1_E202_R 0.609 HLA-DOA_P594_F 0.612 RARA_E128_R 0.609 CHD2_P451_F 0.611 IGF1R_E186_R 0.609 THBS2_E129_F 0.610 LAMB1_E144_R 0.609 GFI1_P208_R 0.610 TNF_P158_F 0.609 FYN_P352_R 0.610 GLI3_E148_R 0.609 FGF7_P610_F 0.610 PRKCDBP_P352_R 0.609 ISL1_P379_F 0.610 CPA4_P961_R 0.609 ABCA1_P45_F 0.610 GPATC3_P410_R 0.608 BMPR1A_E88_F 0.609 UGT1A1_P315_R 0.608 HTR1B_E232_R 0.609 MXI1_P1269_F 0.608 TWIST1_P355_R 0.609 ERBB4_P255_F 0.608 BMP3_P56_R 0.609 FGF5_P238_R 0.608 NGFB_E353_F 0.609 EPHB2_P165_R 0.608 ABO_P312_F 0.609 GLI2_P295_F 0.608 MPO_P883_R 0.609 SKI_E465_R 0.608 FABP3_P598_F 0.609 HLA-DPA1_P28_R 0.607 HS3ST2_P546_F 0.608 DES_P1006_R 0.607 ODC1_P424_F 0.608 GABRG3_P75_F 0.607 MCAM_P265_R 0.608 NEO1_P1067_F 0.607 MXI1_P1269_F 0.608 PROM1_P44_R 0.607 ETV1_P235_F 0.608 ETS2_P684_F 0.606 PTHR1_E36_R 0.608 MCAM_P169_R 0.606 DCC_P177_F 0.607 SMARCB1_P220_R 0.606 PTHR1_P170_R 0.607 MAPK9_P1175_F 0.606 WNT2B_P1185_R 0.607 TNFSF8_E258_R 0.606 IGSF4C_P533_R 0.607 GNAS_P86_F 0.606 IFNGR2_P377_R 0.607 MYLK_P469_R 0.606 SERPINE1_E189_R 0.607 FANCE_P356_R 0.606 SEMA3C_P642_F 0.607 HDAC7A_P344_F 0.606 CAV2_E33_R 0.607 CTSL_P81_F 0.606 MDR1_seq_42_S30C 0.606 CHGA_P243_F 0.605 MUC1_P191_F 0.606 IL12A_E287_R 0.605 WNT1_E157_F 0.606 BCL3_P1038_R 0.605 PCDH1_P264_F 0.605 ZNF215_P129_R 0.605 DNMT2_P199_F 0.605 APOC2_P377_F 0.605 DAPK1_P345_R 0.605 MLLT3_E93_R 0.604 ETS1_P559_R 0.605 CRIP1_P874_R 0.604 EVI2A_E420_F 0.605 PTPRO_E56_F 0.604 EFNB3_E17_R 0.604 EFNB3_P442_R 0.603 TNFSF8_P184_F 0.604 LCK_E28_F 0.603 B3GALT5_E246_R 0.604 SNURF_P78_F 0.603 ERCC1_P440_R 0.604 NNAT_P544_R 0.603 ABCG2_P310_R 0.604 KCNK4_E3_F 0.603 DAB2_P35_F 0.604 DLC1_P695_F 0.603 CTSL_P264_R 0.603 LYN_P241_F 0.603 LRRC32_P865_R 0.603 HLA-DPA1_E35_R 0.602 ADAMTS12_E52_R 0.603 AIM2_P624_F 0.602 BCL3_P1038_R 0.603 GFAP_P1214_F 0.602 TUSC3_P85_R 0.602 XRCC2_P1077_F 0.602 CSPG2_E38_F 0.602 DDB2_P407_F 0.602 PTPNS1_P301_R 0.602 PECAM1_P135_F 0.601 FGF6_P139_R 0.602 SOX2_P546_F 0.601 SNURF_P78_F 0.602 ETS1_E253_R 0.601 CDH1_P52_R 0.602 SERPINB2_P939_F 0.601 LRRC32_E157_F 0.602 SNRPN_E14_F 0.601 SNRPN_E14_F 0.602 LRRK1_P834_F 0.601 TIMP2_E394_R 0.602 TGFBR3_P429_F 0.601 POMC_P400_R 0.602 FGF12_E61_R 0.601 SGCE_E149_F 0.602 EVI1_E47_R 0.601 BCAM_E100_R 0.601 CHI3L2_E10_F 0.601 SFRP1_P157_F 0.601 MAS1_P469_R 0.600 RRAS_P100_R 0.601 IRF7_E236_R 0.600 FZD9_E458_F 0.601 IGFBP6_E47_F 0.600 IPF1_P234_F 0.601 ADCYAP1_E163_R 0.600 FLT4_P180_R 0.601 ZMYND10_E77_R 0.600 PTPRO_P371_F 0.601 CTNNA1_P382_R 0.599 IMPACT_P186_F 0.601 SEMA3B_E96_F 0.599 MATK_P64_F 0.600 CD34_P780_R 0.599 IFNG_P188_F 0.600 PADI4_P1158_R 0.599 TFPI2_E141_F 0.600 SEMA3F_P692_R 0.599 MMP9_E88_R 0.600 LTA_E28_R 0.599 CHD2_P667_F 0.600 DHCR24_P652_R 0.599 HOXC6_P585_R 0.600 KIAA0125_E29_F 0.599 SMAD4_P474_R 0.600 PAX6_P50_R 0.599 IL16_P93_R 0.600 TNFRSF1B_P167_F 0.598 MYBL2_P211_F 0.600 MMP14_P13_F 0.598 KCNQ1_E349_R 0.600 NOTCH2_P312_R 0.598 VAV2_P1182_F 0.599 LMO2_E148_F 0.598 HIC-1_seq_48_S103_R 0.599 IGFBP1_P12_R 0.598 FGF9_P862_R 0.599 VEGFB_P658_F 0.597 EGR4_E70_F 0.599 MATK_P64_F 0.597 TNFRSF1B_P167_F 0.599 DKFZP564O0823_E45_F 0.597 MAPK4_E273_R 0.599 ICAM1_P119_R 0.597 WT1_E32_F 0.598 CASP6_P201_F 0.597 CD40_E58_R 0.598 XRCC1_P681_R 0.597 IL6_P611_F 0.598 IRF7_P277_R 0.597 EPHX1_P1358_R 0.597 HOXA9_P1141_R 0.597 GAS7_E148_F 0.597 ABCB4_E429_F 0.597 COL18A1_P494_R 0.597 IL2_P607_R 0.597 DLC1_P695_F 0.597 CDKN1A_P242_F 0.597 FLI20712_P984_R 0.597 EDN1_E50_R 0.597 GSTP1_E322_R 0.597 ABCG2_P178_R 0.596 TMEM63A_E63_F 0.597 USP29_P205_R 0.596 LMTK2_P1034_F 0.596 RAB32_P493_R 0.596 MMP2_P303_R 0.596 MYBL2_P354_F 0.596 NOTCH1_E452_R 0.596 TYRO3_P501_F 0.596 TFAP2C_E260_F 0.596 CTSD_P726_F 0.596 RIPK2_E123_F 0.595 CHD2_P451_F 0.595 LIF_P383_R 0.595 BCR_P422_F 0.595 EPS8_E231_F 0.595 MOS_P746_F 0.595 NTRK3_P636_R 0.595 IFNG_E293_F 0.595 DNAJC15_E26_R 0.594 TNFSF10_P2_R 0.595 DIRAS3_P745_F 0.594 C4B_P191_F 0.594 ETS2_P835_F 0.594 YES1_P216_F 0.594 GNG7_E310_R 0.594 DAB2_P468_F 0.594 FGF5_E16_F 0.594 CRIP1_P274_F 0.594 EPHA5_P66_F 0.594 FGF9_P862_R 0.594 ACVR2B_E27_R 0.594 NOTCH1_P1198_F 0.594 IGFBP2_P306_F 0.594 MAP3K8_P1036_F 0.593 ADAMTS12_P250_R 0.594 SNRPN_seq_18_S99_(—) 0.593 EFNA1_P591_R 0.594 PECAM1_E32_R 0.593 COPG2_P298_F 0.594 HOXC6_P456_R 0.593 WNT8B_E487_F 0.594 ZIM3_E203_F 0.593 MKRN3_E144_F 0.593 FGFR3_E297_R 0.593 OPCML_E219_R 0.593 CDH3_P87_R 0.593 MATK_P190_R 0.593 IFNG_P188_F 0.592 EPHB6_E342_F 0.593 MKRN3_E144_F 0.592 TIMP3_P1114_R 0.593 CCNE1_P683_F 0.592 MMP2_E21_R 0.593 SH3BP2_E18_F 0.592 PLSCR3_P751_R 0.592 CASP6_P230_R 0.592 SEMA3B_E96_F 0.592 NDN_E131_R 0.592 TSP50_P137_F 0.592 DNMT3B_P352_R 0.592 ZNF215_P129_R 0.592 CPA4_P1265_R 0.591 DMP1_E194_F 0.592 PITX2_E24_R 0.591 MOS_P27_R 0.592 AIM2_E208_F 0.591 ALPL_P433_F 0.592 NDN_P1110_F 0.590 CPA4_P1265_R 0.591 MYCN_E77_R 0.590 TIMP2_P267_F 0.591 p16_seq_47_S188_R 0.590 EIF2AK2_P313_F 0.591 EPHA1_P119_R 0.590 RBP1_P426_R 0.591 MGMT_P281_F 0.590 ALK_E183_R 0.590 ABCA1_P45_F 0.589 PLAU_P11_F 0.590 VAMP8_P114_F 0.589 TIAM1_P188_R 0.590 PEG3_E496_F 0.589 GJB2_P791_R 0.590 PGR_P790_F 0.589 IL18BP_P51_R 0.590 PKD2_P336_R 0.589 EPHB2_E297_F 0.590 GLI2_E90_F 0.589 EPHA8_P456_R 0.589 RARB_P60_F 0.589 EPHB4_E476_R 0.589 PLG_P370_F 0.589 HTR1B_P222_F 0.589 WNT5A_E43_F 0.588 FGF12_E61_R 0.588 PLAGL1_P334_F 0.588 BCL2L2_E172_F 0.587 WEE1_P924_R 0.588 IHH_P529_F 0.587 IL13_E75_R 0.588 MLLT4_P1400_F 0.587 TUBB3_E91_F 0.588 SLC22A18_P216_R 0.587 MMP9_E88_R 0.587 CSTB_E410_F 0.587 MPO_E302_R 0.587 SEPT5_P464_R 0.587 SMAD2_P708_R 0.587 DLL1_P386_F 0.587 RHOH_P953_R 0.587 SH3BP2_P771_R 0.586 CCND1_P343_R 0.587 SMARCA3_P109_R 0.586 TUBB3_P364_F 0.587 NOTCH3_E403_F 0.586 WRN_P969_F 0.587 FABP3_E113_F 0.586 TDGF1_P428_R 0.587 PPARD_P846_F 0.585 TGFB3_E58_R 0.587 CSF1_P217_F 0.585 MMP9_P237_R 0.587 GLI3_E148_R 0.585 GABRA5_P862_R 0.587 SIN3B_P514_R 0.585 CTTN_E29_R 0.587 CHI3L2_E10_F 0.585 HOXB13_E21_F 0.587 XPC_P226_R 0.585 WRN_E57_F 0.587 ERN1_P809_R 0.585 EIF2AK2_E103_R 0.587 AATK_P709_R 0.584 PTHLH_P15_R 0.586 CDK2_P330_R 0.584 LAT_E46_F 0.586 MSH3_E3_F 0.583 LIF_P383_R 0.586 IL12B_P1453_F 0.583 NQO1_P345_R 0.586 MSH2_P1008_F 0.583 SRC_P164_F 0.586 TIMP3_P690_R 0.583 NKX3-1_P146_F 0.586 APC_P14_F 0.583 INHA_P1144_R 0.586 GABRB3_P92_F 0.583 PIK3R1_P307_F 0.586 IL13_E75_R 0.582 SERPINE1_P519_F 0.586 ITGB4_P517_F 0.582 ITPR2_P804_F 0.585 PEG3_E496_F 0.582 SNRPN_seq_12_S127_F 0.585 SOX17_P287_R 0.582 KRAS_P651_F 0.585 RBP1_E158_F 0.582 PTPN6_E171_R 0.585 DDR2_E331_F 0.581 CD1A_P414_R 0.585 FOSL2_E384_R 0.581 TUSC3_P85_R 0.585 EFNA1_P7_F 0.581 MCC_E23_R 0.585 NFKB1_P496_F 0.580 LYN_E353_F 0.584 TSG101_P139_R 0.580 GNAS_E58_F 0.584 PLXDC2_E337_F 0.580 ERCC6_P698_R 0.584 ICAM1_P119_R 0.580 MAGEL2_E166_R 0.583 LYN_P241_F 0.580 HLA-DOB_P1114_R 0.583 MCM2_P260_F 0.580 HPSE_P29_F 0.583 NRAS_P103_R 0.580 MMP8_E89_R 0.583 FVT1_P225_F 0.580 MAP3K9_E17_R 0.582 ROR1_P6_F 0.580 ACVR2B_E27_R 0.582 TBX1_P885_R 0.579 FGF12_P210_R 0.582 CCND3_P435_F 0.579 JAG2_E54_F 0.582 DIO3_P674_F 0.579 SERPINA5_P156_F 0.582 EYA4_P508_F 0.579 TNK1_P221_F 0.582 EPHB3_P569_R 0.579 TGFBI_P31_R 0.581 TP73_E155_F 0.579 TK1_E47_F 0.581 TGFA_P558_F 0.578 TEK_P526_F 0.581 PLXDC1_E71_F 0.578 IGF1_P933_F 0.581 CASP3_P420_R 0.578 IL11_P11_R 0.581 PLAUR_P82_F 0.578 ACVR1C_P363_F 0.580 IGFBP7_P371_F 0.578 PRSS1_E45_R 0.580 ARNT_P238_R 0.577 LIMK1_P709_R 0.580 MOS_P746_F 0.577 GABRA5_P1016_F 0.580 ABO_E110_F 0.577 ESR1_P151_R 0.580 SEZ6L_P249_F 0.577 GPX1_P194_F 0.580 SLIT2_E111_R 0.577 HBII-52_E142_F 0.580 CTNNB1_P757_F 0.577 IAPP_E280_F 0.580 TEK_P526_F 0.577 LCN2_P141_R 0.580 SEPT9_P374_F 0.577 EPHB4_P313_R 0.580 SNRPN_seq_12_S12 0.577 TSG101_P139_R 0.580 COL1A2_P407_R 0.576 PKD2_P287_R 0.580 NQO1_E74_R 0.576 IL4_P262_R 0.579 RAP1A_P285_R 0.576 PGF_E33_F 0.579 PRDM2_P1340_R 0.576 HOXA11_P92_R 0.579 MMP2_P197_F 0.576 APOC1_P406_R 0.579 ACTG2_P455_R 0.576 SFTPC_E13_F 0.579 MSH3_P13_R 0.576 NFKB1_P336_R 0.579 PTPRG_E40_R 0.576 TRIP6_P1090_F 0.579 IHH_P246_R 0.576 ZP3_E90_F 0.579 CRIP1_P274_F 0.576 CASP2_P192_F 0.578 LAMC1_E466_R 0.576 PARP1_P610_R 0.578 TMEFF2_E94_R 0.575 SHB_P473_R 0.577 CTSL_P81_F 0.575 CCR5_P630_R 0.577 ADCYAP1_P398_F 0.575 EPHA2_P340_R 0.577 JAK2_P772_R 0.575 MYLK_E132_R 0.577 RAB32_P493_R 0.575 SNCG_E119_F 0.577 TCF7L2_P193_R 0.575 IGF1_E394_F 0.577 S100A4_P194_R 0.575 APP_P179_R 0.576 FLT3_E326_R 0.574 PHLDA2_E159_R 0.576 AHR_P166_R 0.574 IFNGR1_P307_F 0.576 AIM2_P624_F 0.574 TGFA_P558_F 0.575 FGFR2_P460_R 0.574 BCL2L2_E172_F 0.575 DDIT3_P1313_R 0.573 INSR_E97_F 0.575 FANCE_P356_R 0.573 TJP1_P390_F 0.575 SEMA3F_P692_R 0.573 ENC1_P484_R 0.575 BDNF_P259_R 0.573 LIF_E208_F 0.575 BMP4_P123_R 0.573 MSH3_E3_F 0.575 GAS1_E22_F 0.573 MTA1_P478_F 0.575 FGF3_P171_R 0.572 SEMA3B_P110_R 0.575 WNT5A_P655_F 0.572 MBD2_P233_F 0.574 AREG_P217_R 0.572 PTPN6_P282_R 0.574 CDC25B_P11_R 0.572 EDNRB_P709_R 0.574 GML_P281_R 0.572 HGF_P1293_R 0.574 DLK1_E227_R 0.572 IGFBP1_E48_R 0.574 FLT1_P615_R 0.572 ARHGAP9_P260_F 0.574 EPHB6_P827_R 0.571 IGFBP3_E65_R 0.573 TFPI2_P9_F 0.571 MLF1_P97_F 0.573 IL8_E118_R 0.571 HLA-DPA1_P205_R 0.573 TIE1_E66_R 0.570 FGR_P39_F 0.573 KLF5_P13_F 0.570 ELL_P693_F 0.573 UNG_P170_F 0.570 SFTPA1_P421_F 0.573 RBP1_P150_F 0.570 WNT2B_P1185_R 0.572 CREB1_P819_F 0.570 ACVR1B_E497_R 0.572 IL12B_E25_F 0.570 APC_P280_R 0.572 IL8_P83_F 0.570 EMR3_P39_R 0.572 SFRP1_E398_R 0.570 EGR4_E70_F 0.571 TYK2_P494_F 0.570 DLC1_E276_F 0.571 CD81_P272_R 0.570 TRPM5_E87_F 0.571 ZNF264_P397_F 0.570 LAMC1_E466_R 0.571 SCGB3A1_E55_R 0.570 NRAS_P103_R 0.571 MLLT6_P957_F 0.570 DST_P262_R 0.571 HOXA11_P698_F 0.569 SHB_P691_R 0.570 SLC22A3_E122_R 0.569 ACVR1C_P115_R 0.570 CDK6_E256_F 0.569 LEFTY2_P561_F 0.570 UGT1A1_P564_R 0.569 IL6_E168_F 0.570 CCND2_P887_F 0.569 EPHB3_P569_R 0.570 CD81_P211_F 0.569 TRIP6_E33_F 0.570 TCF4_P175_R 0.569 LMTK2_P1034_F 0.570 FLT1_P302_F 0.569 PITX2_P183_R 0.570 UBA52_P293_R 0.569 GNMT_E126_F 0.569 FANCA_P1006_R 0.569 KCNQ1_P546_R 0.569 PRKAR1A_P337_R 0.569 TK1_P62_R 0.569 RBL2_P250_R 0.569 PCGF4_P760_R 0.568 AFF3_P122_F 0.569 ICAM1_E242_F 0.568 GSTM1_P363_F 0.569 MYCN_P464_R 0.567 EDNRB_P709_R 0.568 EPHA2_P203_F 0.567 SMARCA3_E20_F 0.568 EXT1_E197_F 0.567 INS_P248_F 0.568 TGFA_P642_R 0.567 PECAM1_P135_F 0.568 RASA1_E107_F 0.567 CDH3_E100_R 0.568 SFTPD_E169_F 0.567 PITX2_E24_R 0.568 CDH1_P52_R 0.567 FER_E119_F 0.568 ARNT_P238_R 0.566 PTGS1_P2_F 0.568 CAV1_P169_F 0.566 CDKN2B_E220_F 0.568 IGFBP6_P328_R 0.566 FGF8_P473_F 0.567 IL17RB_P788_R 0.565 APOC1_P406_R 0.567 PTCH2_E173_F 0.565 SLC5A8_E60_R 0.566 GABRG3_E123_R 0.565 EPHA7_E6_F 0.566 PTEN_P438_F 0.565 PADI4_P1011_R 0.566 CDKN2B_seq_50_S294_F 0.565 EPHB1_E202_R 0.566 INSR_P1063_R 0.565 p16_seq_47_S85_F 0.566 PSCA_E359_F 0.564 CEBPA_P1163_R 0.566 SH3BP2_P771_R 0.564 LMO2_P794_R 0.565 PLAU_P11_F 0.564 PSIP1_P163_R 0.565 IGFBP5_E144_F 0.564 IL1B_P829_F 0.565 PLSCR3_P751_R 0.564 IL12B_P392_R 0.565 MMP14_P208_R 0.564 MAGEL2_P170_R 0.565 CTNNA1_P185_R 0.564 EVI2A_P94_R 0.565 HBII-13_P991_R 0.563 ALPL_P278_F 0.565 PWCR1_E81_R 0.563 TFRC_P414_R 0.564 BMP6_P398_F 0.563 HHIP_E94_F 0.564 COL1A2_P407_R 0.563 ZNF264_E48_R 0.564 TFAP2C_E260_F 0.563 NTRK2_P395_R 0.564 KRT1_P798_R 0.563 PMP22_P975_F 0.564 CYP1A1_P382_F 0.563 EYA4_P794_F 0.564 LOX_P71_F 0.562 IGF2_P1036_R 0.564 DMP1_P134_F 0.562 NAT2_P11_F 0.563 P2RX7_E323_R 0.562 CDC25B_E83_F 0.563 CTLA4_P1128_F 0.562 MAPK12_P416_F 0.563 DLC1_P88_R 0.562 DSP_P440_R 0.563 C4B_E171_F 0.562 TNFRSF10C_P612_R 0.563 RHOC_P536_F 0.562 GNG7_P903_F 0.563 CARD15_P665_F 0.561 TNK1_P221_F 0.563 IGF1R_P325_R 0.561 VEGFB_P658_F 0.562 TGFBR3_E188_R 0.561 CHGA_E52_F 0.562 FGF6_P139_R 0.561 APBA2_P227_F 0.562 EFNA1_P591_R 0.561 ISL1_P554_F 0.562 CHI3L2_P226_F 0.561 PRKCDBP_P352_R 0.562 JAK2_P772_R 0.561 MMP9_P237_R 0.561 MLH3_E72_F 0.560 PALM2-AKAP2_P183 0.561 HOXB13_P17_R 0.560 AXL_E61_F 0.561 CDKN1B_P1161_F 0.560 SGCE_P250_R 0.561 DNAJC15_P65_F 0.560 TIAM1_P117_F 0.561 MMP7_E59_F 0.560 PPARG_E178_R 0.561 VAV2_P1182_F 0.560 CTLA4_P1128_F 0.561 IPF1_P234_F 0.560 TFAP2C_P765_F 0.561 ONECUT2_P315_R 0.560 SERPINA5_P156_F 0.561 IL1RN_P93_R 0.559 FRZB_P406_F 0.561 IGFBP3_P423_R 0.559 SOX1_P1018_R 0.560 CSTB_E410_F 0.559 IGF2_P36_R 0.560 JUNB_P1149_R 0.559 PENK_P447_R 0.559 WNT8B_E487_F 0.559 EPM2A_P113_F 0.559 MCM2_P241_R 0.559 RAB32_E314_R 0.559 RUNX1T1_E145_R 0.559 DNAJC15_P65_F 0.559 MAPK4_E273_R 0.558 FGF7_P44_F 0.559 EIF2AK2_P313_F 0.558 EGR4_P479_F 0.559 FYN_P352_R 0.558 WEE1_P924_R 0.559 CDK6_P291_R 0.558 ACTG2_E98_R 0.559 MAP2K6_P297_R 0.558 CDH3_P87_R 0.559 FOSL2_E384_R 0.558 AREG_E25_F 0.558 IL1RN_E42_F 0.558 IFNG_P459_R 0.558 BLK_P668_R 0.557 SEMA3C_E49_R 0.558 IL16_P93_R 0.557 HDAC11_P556_F 0.558 p16_seq_47_S85_F 0.557 C4B_E171_F 0.558 PRSS1_P1249_R 0.557 EPHA7_P205_R 0.558 DDIT3_P1313_R 0.556 LCK_E28_F 0.558 TM7SF3_P1068_R 0.556 TNFRSF10B_P108_R 0.558 FLI20712_P984_R 0.556 OPCML_P71_F 0.558 TFF1_P180_R 0.556 MYH11_P22_F 0.558 MAGEL2_P170_R 0.556 PRSS1_E45_R 0.558 CDK6_E256_F 0.556 HIC2_P528_R 0.558 ID1_P880_F 0.556 THY1_P149_R 0.558 SLC22A2_P109_F 0.556 CEBPA_P706_F 0.557 ITGB4_P517_F 0.556 ABCC2_P88_F 0.557 SPI1_P929_F 0.556 ITPR3_E86_R 0.557 AREG_P217_R 0.555 NOTCH4_E4_F 0.557 CASP10_E139_F 0.555 IL17RB_P788_R 0.557 H19_P541_F 0.555 GFAP_P1214_F 0.557 CSF3R_P472_F 0.555 IGF2_E134_R 0.557 CD9_E14_R 0.555 HOXA9_P303_F 0.557 CAPG_E228_F 0.555 ASB4_P391_F 0.557 HOXA9_E252_R 0.555 PRKCDBP_E206_F 0.556 MAP3K1_P7_F 0.555 PEG10_P978_R 0.556 CDK10_P199_R 0.555 DCC_P471_R 0.556 NEU1_P745_F 0.554 SOX1_P294_F 0.556 CPA4_E20_F 0.554 AGTR1_P154_F 0.556 MAF_P826_R 0.554 NGFR_E328_F 0.556 PTPRF_E178_R 0.554 PENK_E26_F 0.556 PLAT_P80_F 0.554 CCKBR_P361_R 0.555 CPNE1_P138_F 0.554 CDH11_P203_R 0.555 TESK2_P252_R 0.554 ERBB2_P59_R 0.555 HPSE_P93_F 0.554 ITGB1_P451_F 0.555 ROR2_P317_R 0.554 MALT1_P406_R 0.555 S100A12_P1221_R 0.554 IGSF4_P86_R 0.555 YES1_P600_F 0.554 KIT_P405_F 0.555 ID1_P659_R 0.554 IL18BP_E285_F 0.555 PI3_P274_R 0.553 WRN_E57_F 0.555 TCF7L2_E411_F 0.553 FGF5_P238_R 0.554 ZP3_P220_F 0.553 IFNGR2_E164_F 0.554 FANCF_P13_F 0.553 SOX2_P546_F 0.554 LCN2_P86_R 0.552 CFTR_P372_R 0.554 PTK6_E50_F 0.552 COL6A1_P425_F 0.554 HOXA11_P698_F 0.552 LMO1_P169_F 0.554 ARHGDIB_P148_R 0.552 SMARCA3_P17_R 0.553 TNC_P198_F 0.552 IGSF4_P454_F 0.553 FRK_P258_F 0.552 GML_E144_F 0.553 CDH17_P532_F 0.551 RAF1_P330_F 0.553 MUC1_P191_F 0.551 HIC2_P498_F 0.553 IL8_E118_R 0.551 SHH_P104_R 0.553 EGFR_P260_R 0.551 ARHGAP9_P260_F 0.553 LAMC1_P808_F 0.551 TNFRSF1B_E5_F 0.553 TYRO3_P366_F 0.551 FLT3_P302_F 0.553 EPHB4_E476_R 0.550 EDNRB_P148_R 0.553 MEST_E150_F 0.550 CD1A_P6_F 0.553 FER_P581_F 0.550 NFKB2_P709_R 0.552 NRAS_P12_R 0.550 PRSS1_P1249_R 0.552 AGXT_P180_F 0.550 CDKN2B_seq_50_S2 0.552 EFNA1_P7_F 0.549 POMC_P53_F 0.552 HIC1_E151_F 0.549 ZNFN1A1_E102_F 0.552 SRC_P297_F 0.549 EPHA3_P106_R 0.552 ASB4_P52_R 0.549 SLC22A3_P634_F 0.552 FGFR2_P266_R 0.549 CCKAR_P270_F 0.551 IL1B_P829_F 0.548 ASCL2_E76_R 0.551 ICA1_P72_R 0.548 ETS1_E253_R 0.551 FGFR2_P460_R 0.548 MMP7_P613_F 0.550 CREB1_P819_F 0.548 PDGFA_P841_R 0.550 ZIM3_P718_R 0.548 GADD45A_P737_R 0.550 SMARCA4_P362_R 0.547 RASA1_E107_F 0.550 TES_P182_F 0.547 NNAT_P544_R 0.550 ESR2_P162_F 0.547 ERCC3_P1210_R 0.549 DCN_P1320_R 0.547 HGF_E102_R 0.549 TEK_P479_R 0.547 FZD9_P15_R 0.549 CHFR_P501_F 0.546 EVI1_P30_R 0.549 DAPK1_E46_R 0.546 PTK7_E317_F 0.548 CASP3_P420_R 0.546 CTLA4_E176_R 0.548 FGFR3_P1152_R 0.546 PCGF4_P92_R 0.548 PSCA_P135_F 0.546 TDGF1_E53_R 0.548 APBA2_P227_F 0.546 RET_seq_53_S374_F 0.548 ESR2_E66_F 0.546 S100A4_E315_F 0.548 ASB4_E89_F 0.545 EIF2AK2_E103_R 0.548 MMP1_P397_R 0.545 MT1A_E13_R 0.547 MC2R_P1025_F 0.545 ERCC1_P354_F 0.547 NOTCH4_P938_F 0.545 GALR1_P80_F 0.547 RRAS_P100_R 0.545 GSTM1_P266_F 0.547 GFAP_P56_R 0.545 BMPR2_P1271_F 0.547 SEMA3C_E49_R 0.545 EPHB4_P313_R 0.547 CEACAM1_P44_R 0.545 GDF10_P95_R 0.547 MLLT6_P957_F 0.544 OSM_P188_F 0.547 CAV1_P130_R 0.544 HDAC9_E38_F 0.547 MALT1_P406_R 0.544 CD9_E14_R 0.546 HTR2A_P853_F 0.544 CTGF_P693_R 0.546 SERPINA5_E69_F 0.544 SEZ6L_P299_F 0.546 TSC2_E140_F 0.544 EGF_E339_F 0.546 BMP3_P56_R 0.544 APP_E8_F 0.545 PTK7_E317_F 0.544 MPL_P62_F 0.545 JAG1_P66_F 0.544 PALM2-AKAP2_P42C 0.545 NES_P239_R 0.544 PDGFA_P78_F 0.545 GADD45A_P737_R 0.544 SOD3_P460_R 0.545 PLAU_P176_R 0.544 PAX6_P50_R 0.544 CDK10_E74_F 0.544 SMAD2_P708_R 0.544 RARRES1_E235_F 0.543 CASP2_P192_F 0.544 CDH17_P376_F 0.543 PGR_P790_F 0.544 TRPM5_P721_F 0.543 FAT_P279_R 0.544 MCM6_E136_F 0.543 ZP3_E90_F 0.544 CSK_P740_R 0.543 YES1_P216_F 0.543 MMP3_P55_F 0.543 EPHA8_P256_F 0.543 WNT5A_P655_F 0.542 DES_E228_R 0.543 EPHB6_P827_R 0.542 WT1_P853_F 0.543 CDH17_E31_F 0.542 HDAC9_P137_R 0.543 CAV2_E33_R 0.542 WNT10B_P993_F 0.543 BRCA1_P835_R 0.542 KLK11_P103_R 0.542 PHLDA2_P622_F 0.542 COMT_E401_F 0.542 EPM2A_P64_R 0.542 THBS1_P500_F 0.542 ERCC1_P440_R 0.541 DIRAS3_E55_R 0.542 SRC_E100_R 0.541 MYCL1_P502_R 0.542 SMARCA3_E20_F 0.541 RUNX1T1_P103_F 0.542 CTSH_E157_R 0.541 PDE1B_E141_F 0.542 ETS2_P835_F 0.541 PURA_P928_R 0.542 CYP2E1_E53_R 0.541 BDNF_E19_R 0.542 RARRES1_P57_R 0.541 MAPK12_E165_R 0.541 PDGFA_P78_F 0.541 ONECUT2_E96_F 0.541 TRIM29_P135_F 0.540 ID1_P880_F 0.541 TMEM63A_E63_F 0.540 TAL1_P817_F 0.541 TES_E172_F 0.540 ACVR2B_P676_F 0.541 FANCG_E207_R 0.540 CFTR_P115_F 0.541 MMP10_E136_R 0.539 CCL3_P543_R 0.541 KIAA1804_P689_R 0.539 COL6A1_P283_F 0.541 PEG10_P978_R 0.539 FLT4_E206_F 0.541 ABCG2_P310_R 0.539 AGXT_P180_F 0.541 CLDN4_P1120_R 0.539 MAGEL2_E166_R 0.541 MXI1_P75_R 0.539 HHIP_P307_R 0.540 TNFRSF10B_E198_R 0.539 CD86_P3_F 0.540 CDKN2A_E121_R 0.539 TRPM5_E87_F 0.540 CD82_P557_R 0.538 IL17RB_E164_R 0.540 CTSH_P238_F 0.538 TES_E172_F 0.540 HFE_E273_R 0.538 KIT_P367_R 0.540 AFP_P824_F 0.538 ISL1_E87_R 0.540 PTPNS1_E433_R 0.538 APOC2_P377_F 0.540 TSG101_P257_R 0.538 HGF_P1293_R 0.540 TYK2_P494_F 0.537 TNC_P198_F 0.540 CYP2E1_P416_F 0.537 CYP1B1_P212_F 0.539 AXL_P223_R 0.537 ST6GAL1_P164_R 0.539 PTPRH_E173_F 0.537 MAD2L1_E93_F 0.539 FVT1_P225_F 0.537 NTRK1_E74_F 0.539 SERPINB5_P19_R 0.537 MME_E29_F 0.539 PWCR1_P811_F 0.537 PTPRG_P476_F 0.538 ZMYND10_P329_F 0.537 MYBL2_P354_F 0.538 IHH_P529_F 0.537 LTB4R_E64_R 0.538 B3GALT5_E246_R 0.537 JAG1_P66_F 0.538 PGF_P320_F 0.536 IL4_P262_R 0.538 ITGA6_P298_R 0.536 HOXB13_E21_F 0.538 ACVR1B_P572_R 0.536 FGF8_E183_F 0.538 IL12B_P392_R 0.536 HPSE_P29_F 0.538 GJB2_E43_F 0.536 MME_P388_F 0.538 GRB7_E71_R 0.535 LAT_E46_F 0.537 GML_P281_R 0.535 LIG4_P194_F 0.537 JAG2_P264_F 0.535 HSD17B12_E145_R 0.537 GNMT_P197_F 0.535 KRAS_E82_F 0.537 CASP10_P186_F 0.535 LEFTY2_P561_F 0.537 NOS2A_E117_R 0.534 DIO3_P90_F 0.537 KLK11_P1290_F 0.534 TNF_P158_F 0.537 DDB2_P613_R 0.534 RHOC_P536_F 0.537 SYK_E372_F 0.534 TNFSF10_E53_F 0.537 DAB2_P35_F 0.534 THPO_P585_R 0.536 MCC_P196_R 0.534 TPEF_seq_44_S36_F 0.536 HLA-DRA_P132_R 0.534 PTCH2_P37_F 0.536 AFF3_P808_F 0.534 BMP3_E147_F 0.536 SEPT9_P58_R 0.534 APBA1_P644_F 0.536 PRSS8_E134_R 0.534 YES1_P600_F 0.535 KLK11_P103_R 0.533 TM7SF3_P1068_R 0.535 PI3_P1394_R 0.533 COL18A1_P365_R 0.535 ITGA2_P26_R 0.533 ICAM1_E242_F 0.535 BMPR2_E435_F 0.533 BCL2A1_P1127_R 0.534 RUNX3_E27_R 0.533 RARRES1_P57_R 0.534 GPX1_E46_R 0.533 GUCY2D_E419_R 0.534 GAS1_E22_F 0.533 TUBB3_P721_R 0.534 SPDEF_P6_R 0.533 EMR3_P1297_R 0.534 IL12B_E25_F 0.533 HTR2A_P853_F 0.534 MMP3_P16_R 0.532 GJB2_E43_F 0.534 CTSL_P264_R 0.532 ASCL2_P360_F 0.533 SMARCA3_P17_R 0.532 FLI1_E29_F 0.533 APBA1_P644_F 0.532 SERPINB2_P939_F 0.533 BCL2L2_P280_F 0.532 TESK2_P252_R 0.533 IGF2R_P396_R 0.532 FN1_E469_F 0.533 ERCC1_P354_F 0.532 ELK3_P514_F 0.532 ABL1_P53_F 0.532 CALCA_E174_R 0.532 HLA-DPB1_E2_R 0.532 FOLR1_E368_R 0.532 BIRC5_E89_F 0.531 POMC_E254_F 0.532 MAPK12_P416_F 0.531 PHLDA2_E159_R 0.532 CTLA4_E176_R 0.531 CDKN1C_P626_F 0.532 MEST_P4_F 0.531 PODXL_P1341_R 0.532 HLA-DQA2_P282_R 0.531 AFP_P824_F 0.531 FAS_P65_F 0.531 CRIP1_P874_R 0.531 FGF9_P1404_F 0.531 TNC_P57_F 0.531 PSIP1_P163_R 0.531 ROR2_E112_F 0.531 TNFRSF10A_P91_F 0.531 CTTN_E29_R 0.531 NBL1_E205_R 0.531 MTA1_P478_F 0.531 RBL2_P250_R 0.531 TWIST1_P44_R 0.531 SFN_P248_F 0.530 PLAGL1_E68_R 0.531 MET_E333_F 0.530 PLAGL1_P334_F 0.531 BCL3_E71_F 0.530 NTRK2_P10_F 0.531 DDR1_E23_R 0.530 NTRK3_P752_F 0.531 EDNRB_P148_R 0.530 NRAS_P12_R 0.531 PCDH1_P264_F 0.530 EGFR_E295_R 0.531 ATP10A_P524_R 0.530 RASGRF1_E16_F 0.531 ICAM1_P386_R 0.530 FGF12_P210_R 0.530 ITK_P114_F 0.530 ERBB3_P870_R 0.530 BAX_E281_R 0.529 CDKN1A_E101_F 0.530 DAPK1_P10_F 0.529 HRASLS_E72_R 0.530 SNRPN_P230_R 0.529 CASP10_E139_F 0.530 EPHA1_E46_R 0.529 SPARC_P195_F 0.530 COL6A1_P283_F 0.529 EPO_E244_R 0.530 SEMA3A_P343_F 0.529 TP73_P496_F 0.530 NOTCH3_P198_R 0.529 HLA-DPB1_E2_R 0.529 EMR3_E61_F 0.529 HOXA11_P92_R 0.529 S100A2_P1186_F 0.529 KRT1_P798_R 0.529 INHA_P1189_F 0.529 PTHLH_E251_F 0.529 SPP1_P647_F 0.529 GABRB3_E42_F 0.529 PTHR1_P258_F 0.528 CASP6_P201_F 0.528 VAV2_E58_F 0.528 PDGFB_E25_R 0.528 DLL1_P386_F 0.528 CCNE1_P683_F 0.528 DNMT1_P100_R 0.528 HLA-DOB_P1114_R 0.528 HOXA9_P303_F 0.528 PLXDC2_P914_R 0.528 TRIP6_P1274_R 0.528 PTGS2_P308_F 0.528 PPARG_P693_F 0.528 DDB2_P613_R 0.528 HDAC5_E298_F 0.528 CCKBR_P480_F 0.528 VAMP8_P241_F 0.527 SEPT5_P441_F 0.528 DUSP4_E61_F 0.527 JAK3_P156_R 0.528 IL12B_P1453_F 0.527 PWCR1_P357_F 0.528 DSC2_E90_F 0.527 MXI1_P75_R 0.528 CCKAR_P270_F 0.527 PECAM1_E32_R 0.527 KLF5_P13_F 0.526 BCL3_E71_F 0.527 FANCA_P1006_R 0.526 SLC5A5_E60_F 0.527 CD81_P272_R 0.526 MPO_E302_R 0.527 CARD15_P302_R 0.526 PTHLH_P15_R 0.526 RARRES1_P426_R 0.525 IL11_P11_R 0.526 ITGB1_P451_F 0.525 HDAC7A_P344_F 0.526 CDH1_P45_F 0.525 VAV1_E9_F 0.526 ACVR2B_P676_F 0.525 ETV1_P515_F 0.526 SLC22A2_E271_R 0.525 PPP2R1B_P268_R 0.526 ERBB3_E331_F 0.525 BMP6_P163_F 0.526 BMPR2_P1271_F 0.525 STK11_P295_R 0.526 SPDEF_E116_R 0.525 IGFBP3_P423_R 0.525 TNFSF10_E53_F 0.525 ICAM1_P386_R 0.525 DHCR24_P406_R 0.525 CTSH_E157_R 0.525 PPP2R1B_P268_R 0.524 HHIP_P578_R 0.525 HIC1_P565_R 0.524 PDGFRB_E195_R 0.525 SIN3B_P607_F 0.524 TRIP6_E33_F 0.524 MAD2L1_E93_F 0.524 PCGF4_P760_R 0.524 FRK_P36_F 0.524 S100A4_P887_R 0.524 PGR_P456_R 0.524 RUNX3_P393_R 0.524 MKRN3_P108_F 0.524 ARHGAP9_P518_R 0.524 IHH_E186_F 0.524 KLK11_P1290_F 0.524 WNT2B_P1195_F 0.524 DNMT1_P100_R 0.523 RUNX1T1_P103_F 0.524 SHB_P473_R 0.523 TNFRSF10B_P108_R 0.523 MLF1_P97_F 0.523 EDN1_P39_R 0.523 ASCL1_E24_F 0.523 CXCL9_E268_R 0.523 DMP1_P134_F 0.523 PLAUR_E123_F 0.523 FLT1_E444_F 0.523 TMEFF1_P234_F 0.523 ESR1_P151_R 0.523 CREBBP_P712_R 0.523 MAP3K1_E81_F 0.523 TRAF4_P372_F 0.523 ST6GAL1_P528_F 0.523 BMP2_E48_R 0.523 EPHA3_E156_R 0.523 IGSF4C_E65_F 0.522 FGR_P39_F 0.523 EGFR_E295_R 0.522 SEMA3A_P343_F 0.523 AHR_E103_F 0.522 CAV1_P130_R 0.523 EFNB3_E17_R 0.522 KDR_E79_F 0.522 CDKN1C_P6_R 0.522 WNT10B_P823_R 0.522 DUSP4_P925_R 0.522 CDK6_P291_R 0.522 PXN_P308_F 0.522 GPR116_P850_F 0.522 AXL_E61_F 0.521 CDKN1B_P1161_F 0.521 MUSK_P308_F 0.521 ONECUT2_P315_R 0.521 MAPK14_P327_R 0.521 PLAGL1_P236_R 0.521 LMO1_P169_F 0.521 GSTP1_seq_38_S15$$ 0.521 NBL1_P24_F 0.521 MCM6_E136_F 0.521 KCNQ1_E349_R 0.521 PLAU_P176_R 0.521 BCAM_P205_F 0.521 ELL_P693_F 0.521 NID1_P677_F 0.521 ADCYAP1_E163_R 0.520 TJP1_P326_R 0.521 CDKN2A_E121_R 0.520 ERBB3_P870_R 0.521 PDGFRA_E125_F 0.520 FZD7_E296_F 0.520 TK1_E47_F 0.520 ONECUT2_E96_F 0.520 KDR_P445_R 0.520 HRASLS_E72_R 0.520 S100A12_P1221_R 0.520 CD81_P211_F 0.520 GABRA5_P1016_F 0.520 HOXA11_E35_F 0.520 FGF9_P1404_F 0.520 ETV6_E430_F 0.520 ESR2_E66_F 0.520 CASP8_E474_F 0.520 CCND2_P898_R 0.519 PTGS2_P308_F 0.520 WRN_P969_F 0.519 FER_E119_F 0.520 ITGA6_P298_R 0.519 MMP1_P460_F 0.520 EPHA5_E158_R 0.519 HTR2A_E10_R 0.520 SLC22A2_P109_F 0.519 TNFRSF10A_P171_F 0.519 MYOD1_P50_F 0.519 CCL3_E53_R 0.519 BIRC5_E89_F 0.519 ASB4_P391_F 0.519 NGFR_P355_F 0.519 ITGA2_E120_F 0.519 IGFBP5_E144_F 0.519 DDR1_P332_R 0.519 NRG1_E74_F 0.519 PROK2_E0_F 0.519 ASCL1_P747_F 0.519 NTRK1_E74_F 0.519 ACTG2_P346_F 0.518 TIMP2_E394_R 0.518 LTA_E28_R 0.518 TIMP3_P1114_R 0.518 SFTPA1_P421_F 0.518 SMAD4_P474_R 0.518 GABRA5_P862_R 0.518 EPHB3_E0_F 0.518 IMPACT_P234_R 0.518 HIF1A_P488_F 0.518 TPEF_seq_44_S88_R 0.518 CASP10_P334_F 0.518 CASP6_P230_R 0.517 CEACAM1_E57_R 0.518 TNFRSF10B_E198_R 0.517 RYK_P493_F 0.518 RYK_P493_F 0.517 ROR1_P6_F 0.518 HBII-13_E48_F 0.517 PTK2B_P673_R 0.518 CCKAR_E79_F 0.517 NEFL_E23_R 0.517 COL1A1_P117_R 0.517 EMR3_P1297_R 0.517 CCR5_P630_R 0.517 PPARG_E178_R 0.517 APOA1_P75_F 0.517 CCND1_E280_R 0.517 VAV2_E58_F 0.516 STK11_P295_R 0.517 HTR2A_E10_R 0.516 HDAC1_P414_R 0.517 WNT2_P217_F 0.516 E2F3_P840_R 0.517 PLG_E406_F 0.516 TRIM29_E189_F 0.516 NDN_P1110_F 0.516 CRK_P721_F 0.516 DCC_E53_R 0.516 RAD54B_P227_F 0.516 PROK2_P390_F 0.516 LIG3_P622_R 0.516 LTA_P214_R 0.516 CCKAR_E79_F 0.516 DAB2IP_P9_F 0.516 BCL2A1_P1127_R 0.516 RET_seq_54_S260_F 0.516 ABCC5_P444_F 0.516 TIMP3_seq_7_S38_F 0.516 PWCR1_P357_F 0.516 FN1_P229_R 0.515 SEMA3F_E333_R 0.515 DSC2_P407_R 0.515 THBS1_P500_F 0.515 WNT1_P79_R 0.515 ABCC2_P88_F 0.515 H19_P1411_R 0.515 MAP3K1_E81_F 0.515 TEK_P479_R 0.515 ITPR3_E86_R 0.515 TAL1_E122_F 0.515 NR2F6_E375_R 0.515 SPARC_E50_R 0.515 MYCL1_P502_R 0.514 TRAF4_P372_F 0.515 USP29_E274_F 0.514 LOX_P71_F 0.515 MAF_E77_R 0.514 PI3_E107_F 0.515 CSF1_P217_F 0.514 FGFR1_P204_F 0.514 OGG1_E400_F 0.514 DDB2_P407_F 0.514 PLAUR_P82_F 0.514 GUCY2D_P48_R 0.514 E2F5_P516_R 0.514 IGSF4C_E65_F 0.514 EPM2A_P113_F 0.514 PTHLH_P757_F 0.514 CDKN2B_E220_F 0.514 ABL2_P459_R 0.513 SIN3B_P514_R 0.514 AHR_E103_F 0.513 EPS8_E231_F 0.513 ALK_P28_F 0.513 IHH_P246_R 0.513 APP_P179_R 0.513 RIPK4_P172_F 0.513 EPHB1_P503_F 0.513 GABRA5_E44_R 0.513 HTR1B_P107_F 0.513 TMEFF1_E180_R 0.513 PGR_P456_R 0.513 ZNFN1A1_E102_F 0.512 MAS1_P469_R 0.513 PCGF4_P92_R 0.512 CALCA_P75_F 0.513 CDH3_E100_R 0.512 ZIM2_E110_F 0.513 PGR_E183_R 0.512 PDGFRB_P343_F 0.513 AFF3_P122_F 0.512 HOXA11_E35_F 0.513 HBII-13_E48_F 0.512 DES_P1006_R 0.513 HBEGF_P32_R 0.512 DDR1_E23_R 0.512 MAP2K6_E297_F 0.512 MLF1_E243_F 0.512 TNK1_P41_R 0.511 CHI3L2_P226_F 0.512 RIPK4_E166_F 0.511 ABL1_P53_F 0.512 ABCC2_E16_R 0.511 MAP2K6_E297_F 0.512 HLA-DQA2_E93_F 0.511 ESR2_P162_F 0.512 SEPT5_P464_R 0.510 JAK3_E64_F 0.512 C20orf47_P225_R 0.510 OSM_P34_F 0.512 ZNFN1A1_P179_F 0.510 APC_P280_R 0.511 TDG_E129_F 0.510 CYP2E1_P416_F 0.511 TFRC_P414_R 0.510 CARD15_P665_F 0.511 SMAD2_P848_R 0.510 NTRK3_E131_F 0.511 IGFBP3_P1035_F 0.510 EPO_P162_R 0.511 TIMP3_P690_R 0.510 FGFR3_P1152_R 0.511 ZNF264_E48_R 0.510 ABCB4_E429_F 0.511 MPO_P883_R 0.510 MYLK_E132_R 0.511 COPG2_P298_F 0.510 KIAA0125_E29_F 0.511 RAF1_P330_F 0.510 CTSH_P238_F 0.510 TFF2_P178_F 0.510 SNURF_E256_R 0.510 HGF_E102_R 0.510 LAMC1_P808_F 0.510 BCL6_P248_R 0.509 PMP22_P1254_F 0.510 DSG1_P159_R 0.509 HLA-DRA_P77_R 0.510 PADI4_P1011_R 0.509 TWIST1_E117_R 0.510 FASTK_P257_F 0.509 FZD9_P175_F 0.510 INS_P248_F 0.509 IGF1_P933_F 0.509 HBII-52_P563_F 0.509 PROK2_E0_F 0.509 VAMP8_E7_F 0.509 CCNA1_P216_F 0.509 NFKB2_P709_R 0.509 SLC5A8_P38_R 0.509 TGFBI_P173_F 0.509 PGR_E183_R 0.509 DSP_P440_R 0.509 INSR_P1063_R 0.509 APBA1_E99_R 0.509 CDH1_P45_F 0.508 MUC1_E18_R 0.509 MAF_E77_R 0.508 NOS3_P38_F 0.509 CHFR_P501_F 0.508 SNCG_P53_F 0.508 EPM2A_P64_R 0.508 LIG4_P194_F 0.508 NRG1_P558_R 0.508 NQO1_E74_R 0.508 ABCA1_E120_R 0.508 BMPR1A_P956_F 0.508 NPY_P91_F 0.508 UNG_P170_F 0.508 RARB_P60_F 0.508 SEPT5_P441_F 0.508 DUSP4_P925_R 0.508 IRF5_P123_F 0.508 F2R_P839_F 0.507 IMPACT_P186_F 0.508 FANCG_E207_R 0.507 MGMT_P272_R 0.507 LRRK1_P834_F 0.507 NOTCH1_E452_R 0.507 GFAP_P56_R 0.507 H19_P1411_R 0.507 SOD3_P225_F 0.507 SFN_E118_F 0.507 GFI1_E136_F 0.507 PTPRH_P255_F 0.507 FLI1_P620_R 0.507 UBA52_P293_R 0.507 AGTR1_P41_F 0.507 GRB7_P160_R 0.507 ZIM2_P22_F 0.507 COL6A1_P425_F 0.507 C20orf47_P225_R 0.506 IL8_P83_F 0.507 PTCH2_P568_R 0.506 FN1_P229_R 0.507 HCK_P46_R 0.506 AGXT_E115_R 0.506 CSF3R_P472_F 0.506 GAS1_P754_R 0.506 LAMB1_E144_R 0.506 CCND3_P435_F 0.506 THY1_P20_R 0.506 PRKAR1A_P337_R 0.506 MEG3_P235_F 0.505 MCM2_P260_F 0.506 COL4A3_E205_R 0.505 AREG_E25_F 0.505 ACVR1B_E497_R 0.505 NCL_P840_R 0.505 FZD7_E296_F 0.505 MDS1_E45_F 0.505 RARB_E114_F 0.505 EVI1_P30_R 0.505 C4B_P191_F 0.505 PTGS1_P2_F 0.505 IGFBP3_P1035_F 0.504 DSP_P36_F 0.504 CSF3_E242_R 0.504 FGF6_E294_F 0.504 MLLT3_E93_R 0.504 HLA-DRA_P77_R 0.504 CDH11_E102_R 0.504 CDK2_P330_R 0.503 TES_P182_F 0.504 FAT_P973_R 0.503 IHH_E186_F 0.504 ITPR3_P1112_F 0.503 CDH17_P532_F 0.504 AHR_P166_R 0.502 IL6_P213_R 0.504 RIPK2_E123_F 0.502 TMEFF1_E180_R 0.504 ABL2_P459_R 0.502 ITGA2_P26_R 0.502 ODC1_P424_F 0.502 DSG1_E292_F 0.502 EPHB2_E297_F 0.502 HOXB13_P17_R 0.502 PTK2_P735_R 0.502 FASTK_P257_F 0.502 KLF5_E190_R 0.502 NES_P239_R 0.502 IL6_P611_F 0.502 PIK3R1_P307_F 0.502 FAT_P279_R 0.502 IL10_P85_F 0.502 ERBB2_P59_R 0.502 ADCYAP1_P455_R 0.502 MEST_P62_R 0.502 DBC1_P351_R 0.502 APP_E8_F 0.502 NGFB_P13_F 0.501 TCF7L2_P193_R 0.502 FGF3_E198_R 0.501 CD1A_P6_F 0.501 PDE1B_P263_R 0.501 PDGFB_E25_R 0.501 SMARCA4_P362_R 0.501 CTGF_P693_R 0.501 MGMT_P272_R 0.501 CEBPA_P706_F 0.501 SERPINA5_E69_F 0.500 SNURF_E256_R 0.501 HBEGF_P32_R 0.500 ITK_E166_R 0.501 INS_P804_R 0.500 HDAC11_P556_F 0.501 INSR_E97_F 0.500 ICA1_P61_F 0.500 GPATC3_P410_R 0.500 EGR4_P479_F 0.500

SUPPLEMENTAL TABLE 17 Rank ordered list of most critical CpG loci for differentiating invasive bladder tumors from non invasive bladder tumors by Random Forests classification in both tumor series. Series 1 Series 2 GENE_CpG Percent Increase in MSE GENE_CpG Percent Increase in MSE SLC14A1_E295_F 20.08 STAT5A_P704_R 26.77 EGF_P413_F 17.21 KRT13_P341_R 23.93 RARA_P1076_R 16.33 CDH11_E102_R 23.60 JAG2_P264_F 16.04 GP1BB_P278_R 23.24 STAT5A_P704_R 15.28 RASSF1_E116_F 22.35 FRZB_E186_R 15.22 HOXB2_P488_R 22.06 SIN3B_P607_F 14.43 SLIT2_E111_R 21.35 HS3ST2_P171_F 14.19 FGF3_E198_R 20.72 TEK_E75_F 14.18 SEPT9_P374_F 20.45 MDR1_seq_42_S300_R 13.89 HS3ST2_P171_F 20.21 SLC14A1_P369_R 13.57 RIPK1_P868_F 20.19 RIPK1_P868_F 13.05 HPN_P374_R 19.92 UGT1A1_P315_R 12.98 FLT1_E444_F 19.69 CSF1R_P73_F 12.75 TPEF_seq_44_S36_F 19.00 AATK_E63_R 12.64 TERT_P360_R 18.01 MAD2L1_E93_F 12.51 FGF1_P357_R 17.81 AATK_P519_R 12.43 TERT_E20_F 17.76 CSF1R_E26_F 12.37 GAS7_P622_R 17.49 FGF1_P357_R 12.27 SLIT2_P208_F 17.33 GABRG3_P75_F 12.25 DIO3_P90_F 17.14 ZIM2_P22_F 12.16 CDH11_P203_R 17.02 RARA_P176_R 11.83 NOTCH4_E4_F 16.91 IRF5_P123_F 11.39 OPCML_E219_R 16.80 SPP1_E140_R 11.35 RARA_P1076_R 16.62 TAL1_E122_F 11.26 CSPG2_P82_R 16.23 KRT13_P341_R 11.23 CHGA_E52_F 16.13 THBS2_P605_R 11.09 VIM_P343_R 15.96 HPN_P374_R 11.01 FLT4_E206_F 15.73 MMP3_P16_R 10.90 MST1R_E42_R 15.71 FGFR4_P610_F 10.57 CSF3_P309_R 15.56 CHI3L2_P226_F 10.53 FGF3_P171_R 15.50 KLK10_P268_R 10.29 SFRP1_E398_R 15.49 IGSF4_P454_F 10.19 EPHA5_E158_R 15.31 CSF2_P605_F 10.10 FGF1_E5_F 15.19 CALCA_P75_F 9.99 EYA4_E277_F 15.00 USP29_P282_R 9.59 RASSF1_P244_F 14.98 HS3ST2_P546_F 9.59 IRAK3_P13_F 14.90 DDIT3_P1313_R 9.52 HHIP_E94_F 14.86 TRPM5_P979_F 9.20 IGFBP7_P297_F 14.85 SNCG_E119_F 8.94 GDF10_P95_R 14.43 TIMP3_seq_7_S38_F 8.74 NPY_E31_R 14.32 EPHA1_P119_R 8.73 CDH13_E102_F 14.27 FRZB_P406_F 8.66 DES_E228_R 14.22 MAP3K1_P7_F 8.53 IRF7_E236_R 14.03 CSF3_P309_R 8.45 PROK2_P390_F 13.99 EPM2A_P64_R 8.34 SFRP1_P157_F 13.76 HOXB2_P488_R 8.32 THY1_P149_R 13.71 UGT1A1_E11_F 8.19 TNFRSF10C_P7_F 13.67 PLAGL1_P334_F 8.08 NGFB_E353_F 13.56 MMP7_E59_F 8.06 AGTR1_P41_F 13.32 IGFBP3_P1035_F 7.92 SPP1_E140_R 13.18 TMPRSS4_E83_F 7.83 EYA4_P508_F 13.18 EPHA2_P340_R 7.75 GUCY2D_E419_R 13.09 GPR116_E328_R 7.68 PALM2-AKAP2_P183_R 13.08 SMO_E57_F 7.66 LY6G6E_P45_R 13.04 NRG1_P558_R 7.62 PADI4_P1158_R 12.63 HIC-1_seq_48_S103_R 7.57 ACVR1_P983_F 12.33 ITK_E166_R 7.55 HTR1B_P222_F 12.09 TUSC3_E29_R 7.50 NTSR1_P318_F 12.00 PTPRO_P371_F 7.45 VAV1_E9_F 11.93 GP1BB_E23_F 7.35 MST1R_P392_F 11.87 AFF3_P808_F 7.33 ADCYAP1_E163_R 11.86 SPI1_P929_F 7.30 MYH11_P236_R 11.74 RARB_E114_F 7.29 CD9_P504_F 11.65 BMP2_P1201_F 7.28 SOX1_P294_F 11.64 SNCG_P53_F 7.27 APBA2_P305_R 11.56 IGFBP2_P306_F 7.20 MMP2_P197_F 11.46 COL18A1_P365_R 7.11 SMO_E57_F 11.43 CSPG2_E38_F 7.11 CDH13_P88_F 11.21 HOXA5_P479_F 6.91 FRZB_P406_F 11.16 EVI2A_P94_R 6.89 STAT5A_E42_F 10.99 TJP2_P518_F 6.82 SIN3B_P607_F 10.94 FASTK_P598_R 6.79 HRASLS_P353_R 10.80 MAS1_P657_R 6.79 ETV1_P235_F 10.73 FGF1_E5_F 6.78 UGT1A1_E11_F 10.70 KRT13_P676_F 6.65 TEK_E75_F 10.65 NPR2_P1093_F 6.60 NTSR1_E109_F 10.64 ERG_E28_F 6.57 FGF12_E61_R 10.60 HOXB2_P99_F 6.53 NTRK3_P752_F 10.52 DUSP4_E61_F 6.47 FRZB_E186_R 10.52 NID1_P714_R 6.45 SLC5A8_E60_R 10.41 USP29_P205_R 6.43 PPARG_P693_F 10.38 VIM_P811_R 6.42 PTPRG_P476_F 10.09 PSCA_P135_F 6.40 GSTM2_P109_R 10.05 AIM2_E208_F 6.36 EPO_E244_R 10.04 ALOX12_E85_R 6.35 FGFR4_P610_F 10.04 DMP1_P134_F 6.29 SLC5A5_E60_F 10.02 WNT8B_P216_R 6.20 PYCARD_P150_F 9.99 ZIM3_E203_F 6.20 FABP3_P598_F 9.92 RARRES1_E235_F 6.14 ACVR1_E328_R 9.92 SEZ6L_P299_F 6.11 KRT13_P676_F 9.88 CSPG2_P82_R 6.11 POMC_P400_R 9.76 MUC1_E18_R 6.09 USP29_E274_F 9.73 OGG1_E400_F 6.09 ISL1_E87_R 9.65 POMC_E254_F 6.09 THY1_P20_R 9.65 ASCL2_E76_R 6.03 TMPRSS4_P552_F 9.58 RARA_E128_R 6.02 IRF7_P277_R 9.55 SPI1_P48_F 5.97 BMP4_P199_R 9.52 DHCR24_P652_R 5.95 S100A4_E315_F 9.48 PLAT_P80_F 5.94 FGF8_P473_F 9.48 PCDH1_E22_F 5.89 SLC14A1_E295_F 9.47 ER_seq_a1_S60_F 5.89 SRC_P297_F 9.37 GP1BB_P278_R 5.88 ASCL2_E76_R 9.30 DNMT3B_P352_R 5.83 DBC1_E204_F 9.29 GUCY2D_E419_R 5.82 NRG1_P558_R 9.20 HLA-DOB_E432_R 5.80 NID1_P714_R 9.07 MFAP4_P10_R 5.80 EYA4_P794_F 9.05 SH3BP2_E18_F 5.79 GALR1_P80_F 9.02 HIC2_P498_F 5.75 TRIP6_P1274_R 8.99 SYK_P584_F 5.74 MT1A_P49_R 8.88 TNFRSF10C_P7_F 5.69 AGTR1_P154_F 8.75 TFF2_P178_F 5.68 MST1R_P87_R 8.73 IGFBP1_P12_R 5.67 FLI1_E29_F 8.67 IRF7_E236_R 5.67 AATK_E63_R 8.66 HFE_E273_R 5.65 EGF_P413_F 8.58 CDH17_P376_F 5.62 NTRK2_P10_F 8.55 CCKAR_E79_F 5.59 ASCL2_P360_F 8.53 ACTG2_P455_R 5.58 TIMP2_P267_F 8.44 AATK_P709_R 5.53 CCKBR_P480_F 8.37 TGFB3_E58_R 5.47 SCGB3A1_E55_R 8.33 HPN_P823_F 5.46 ALOX12_E85_R 8.25 DLL1_P832_F 5.45 TNFRSF10C_E109_F 8.20 MOS_E60_R 5.42 HPN_P823_F 8.19 TNFSF8_E258_R 5.39 GABRG3_P75_F 8.13 THBS1_E207_R 5.35 TGFB2_P632_F 8.02 EPHB2_P165_R 5.32 APC_P280_R 8.00 CFTR_P115_F 5.29 IGFBP2_P306_F 8.00 CDH17_E31_F 5.28 TAL1_E122_F 7.96 PLAGL1_E68_R 5.20 TRIP6_P1090_F 7.94 MMP19_E274_R 5.19 GALR1_E52_F 7.93 CDKN1B_P1161_F 5.17 TFF2_P557_R 7.89 SPDEF_E116_R 5.17 MEG3_E91_F 7.84 ERCC1_P440_R 5.15 IGFBP1_P12_R 7.83 TSC2_E140_F 5.14 IRAK3_E130_F 7.77 CHI3L2_E10_F 5.13 FLI1_P620_R 7.75 UGT1A7_P751_R 5.11 EPHA7_E6_F 7.74 FRK_P258_F 5.10 MFAP4_P197_F 7.70 FLJ20712_P984_R 5.09 SPI1_P48_F 7.65 JAK3_P1075_R 5.06 GFI1_P45_R 7.65 KCNQ1_P546_R 5.02 DCC_P471_R 7.55 ACVR1C_P115_R 5.01 RARA_P176_R 7.54 BMP4_P199_R 5.01 TGFB2_E226_R 7.52 CYP2E1_E53_R 5.00 ISL1_P379_F 7.48 ZMYND10_E77_R 7.45 OPCML_P71_F 7.45 PLXDC2_E337_F 7.44 HOXB2_P99_F 7.41 WNT2_P217_F 7.39 IGF1R_P325_R 7.39 ERBB4_P541_F 7.32 EGF_E339_F 7.22 GSTM2_E153_F 7.21 GAS7_E148_F 7.17 FGF5_E16_F 7.11 TMEFF2_E94_R 7.11 PENK_E26_F 7.09 NOS2A_P288_R 7.08 MKRN3_E144_F 7.08 CSF1R_E26_F 7.07 EPHA2_P340_R 7.05 CD1A_P414_R 7.01 CSF2_P605_F 6.96 TRPM5_P979_F 6.95 MMP9_P189_F 6.89 CCND2_P898_R 6.85 DIO3_P674_F 6.77 WT1_E32_F 6.77 CCND2_P887_F 6.77 CLK1_P538_F 6.76 SGCE_E149_F 6.66 CFTR_P372_R 6.60 FGF5_P238_R 6.53 ZIM3_E203_F 6.51 APC_P14_F 6.50 ABO_P312_F 6.48 TPEF_seq_44_S88_R 6.47 BCR_P422_F 6.46 PAX6_E129_F 6.46 MMP1_P460_F 6.36 HS3ST2_P546_F 6.35 PDE1B_E141_F 6.29 TNFRSF1A_P678_F 6.23 FLT1_P615_R 6.17 HOXA5_E187_F 6.16 HTR1B_E232_R 6.15 ABCB4_E429_F 6.13 IRAK3_P185_F 6.07 MMP9_P237_R 6.06 THBS2_P605_R 6.05 PTHR1_P258_F 5.98 DLK1_E227_R 5.95 GJB2_P791_R 5.95 XRCC1_P681_R 5.94 UGT1A1_P315_R 5.89 JAK3_E64_F 5.86 JAK3_P1075_R 5.84 CALCA_P75_F 5.80 TBX1_P520_F 5.79 TIMP3_seq_7_S38_F 5.78 PRKCDBP_E206_F 5.77 ALOX12_P223_R 5.72 NID1_P677_F 5.68 HBII-52_P659_F 5.61 FGF12_P210_R 5.60 TMPRSS4_E83_F 5.58 TWIST1_E117_R 5.56 MOS_E60_R 5.55 ITK_E166_R 5.51 MT1A_E13_R 5.50 PGR_P456_R 5.50 HHIP_P578_R 5.48 FHIT_P93_R 5.47 GPR116_E328_R 5.43 PLAT_P80_F 5.41 BLK_P668_R 5.36 COL1A2_P48_R 5.35 ETV1_P515_F 5.35 AATK_P709_R 5.34 COMT_E401_F 5.29 NFKB1_P496_F 5.25 FGF2_P229_F 5.25 CDH17_E31_F 5.23 MYOD1_P50_F 5.20 IL18BP_P51_R 5.18 IGF2AS_E4_F 5.17 DCC_E53_R 5.15 SRC_P164_F 5.15 GABRA5_E44_R 5.11 CD34_P780_R 5.10 HS3ST2_E145_R 5.06 PENK_P447_R 5.02

SUPPLEMENTAL TABLE 18 Differential methylation at CpG loci in lung tumor samples versus non tumor lung samples. Regression GENE_CpG coefficient* P-value Q-value Rank CASP8_E474_F −0.93 0 0 1 COMT_E401_F −0.74 0 0 2 DLC1_P695_F −1.21 0 0 3 DLK1_E227_R 1.75 0 0 4 EMR3_P39_R −1.24 0 0 5 EYA4_P794_F 1.12 0 0 6 HCK_P858_F 1.30 0 0 7 HDAC1_P414_R −0.93 0 0 8 HOXA11_P698_F 1.60 0 0 9 HOXA5_P1324_F 1.09 0 0 10 HOXA9_E252_R 2.39 0 0 11 HOXA9_P1141_R 2.06 0 0 12 HOXA9_P303_F 1.27 0 0 13 HTR1B_P222_F 1.99 0 0 14 ID1_P880_F −0.56 0 0 15 IPF1_P750_F 1.28 0 0 16 IRF5_E101_F 1.18 0 0 17 MOS_E60_R 1.74 0 0 18 MUC1_P191_F −1.01 0 0 19 MYOD1_E156_F 1.91 0 0 20 PTPN6_E171_R −1.65 0 0 21 PTPRH_E173_F −1.10 0 0 22 SFN_P248_F −0.98 0 0 23 SOX17_P287_R 1.17 0 0 24 SOX17_P303_F 1.46 0 0 25 TAL1_P594_F 1.81 0 0 26 HS3ST2_E145_R 1.53 0 0 27 PTPN6_P282_R −1.22 0 0 28 RARRES1_P57_R −0.59 0 0 29 MUC1_E18_R −0.80 0 0 30 TMPRSS4_E83_F −1.35 0 0 31 TERT_P360_R 1.62 0 0 32 PRSS1_P1249_R −0.84 0 0 33 HTR1B_E232_R 1.16 0 0 34 TNFSF10_P2_R −1.00 0 0 35 ERBB2_P59_R 1.04 0 0 36 PLA2G2A_P528_F −1.01 0 0 37 NOS3_P38_F −1.02 0 0 38 DIO3_E230_R 0.62 0 0 39 TPEF_seq_44_S88_R 1.52 0 0 40 GABRA5_P862_R −1.30 0 0 41 NID1_P677_F −1.43 0 0 42 MPL_P657_F −0.60 0 0 43 NPY_P295_F 1.59 0 0 44 SOX1_P1018_R 1.85 0 0 45 ITK_P114_F −1.11 0 0 46 FRZB_E186_R 1.39 0 0 47 ADCYAP1_P398_F 1.46 0 0 48 WT1_P853_F 1.55 0 0 49 STAT5A_E42_F 1.02 0 0 50 SPP1_P647_F −0.94 0 0 51 MDR1_seq_42_S300_R 2.13 0 0 52 SPARC_P195_F 0.93 0 0 53 SOX1_P294_F 1.27 0 0 54 DDR1_P332_R −1.03 0 0 55 SERPINB5_P19_R −1.49 0 0 56 NID1_P714_R −0.94 0 0 57 PYCARD_P150_F 0.82 0 0 58 IL16_P93_R −0.79 0 0 59 BCL3_E71_F −0.34 0 0 60 CARD15_P302_R −0.77 0 0 61 APBA1_P644_F 0.30 0 0 62 NEFL_P209_R 1.12 0 0 63 VAMP8_P114_F −0.71 0 0 64 IGF2AS_P203_F 0.87 0 0 65 HOXA11_E35_F 1.23 0 0 66 PITX2_E24_R 1.05 0 0 67 TRIM29_P135_F −0.91 0 0 68 EMR3_E61_F −0.86 0 0 69 RARA_P1076_R 0.92 0 0 70 HS3ST2_P171_F 0.92 0 0 71 GABRG3_P75_F −0.88 0 0 72 AFF3_P122_F −1.17 0 0 73 CDH13_E102_F 1.38 0 0 74 DCC_P471_R 1.15 0 0 75 MEST_P4_F −0.90 0 0 76 CCNE1_P683_F −0.32 0 0 77 PI3_P1394_R −0.87 0 0 78 DCC_E53_R 0.81 0 0 79 MOS_P27_R 0.99 0 0 80 CLDN4_P1120_R −0.78 0 0 81 PRSS1_E45_R −0.75 0 0 82 IFNG_E293_F −0.77 0 0 83 CCR5_P630_R −0.48 0 0 84 WT1_E32_F 1.78 0 0 85 CCL3_E53_R −0.79 0 0 86 GFI1_P45_R 1.00 0 0 87 NOS2A_E117_R −0.95 0 0 88 DBC1_P351_R 1.38 0 0 89 SLIT2_P208_F 1.10 0 0 90 CHD2_P451_F −0.63 0 0 91 FGF2_P229_F 1.05 0 0 92 RUNX3_E27_R −0.78 0 0 93 BAX_E281_R −0.63 0 0 94 PENK_P447_R 1.11 0 0 95 PDGFRA_E125_F 0.76 0 0 96 ATP10A_P524_R −0.67 0 0 97 GML_P281_R −1.23 0 0 98 PTK7_E317_F −0.46 0 0 99 PI3_P274_R −1.03 0 0 100 CALCA_E174_R 1.02 0 0 101 GABRA5_P1016_F −1.20 0 0 102 USP29_E274_F −1.24 0 0 103 GALR1_E52_F 1.07 0 0 104 DCC_P177_F 1.04 0 0 105 CPA4_E20_F −0.67 0 0 106 VAV1_P317_F −0.82 0 0 107 AIM2_P624_F −0.96 0 0 108 ETS2_P835_F −0.49 0 0 109 PENK_E26_F 0.50 0 0 110 PLG_E406_F −0.63 0 0 111 FLT3_E326_R 1.43 0 0 112 THY1_P149_R 1.15 0 0 113 NBL1_P24_F −0.77 0 0 114 GABRG3_E123_R −1.03 0 0 115 CD2_P68_F −0.89 0 0 116 RARB_E114_F 1.68 0 0 117 NOTCH4_P938_F −0.86 0 0 118 EMR3_P1297_R −0.98 0 0 119 NEO1_P1067_F −0.64 0 0 120 ZMYND10_P329_F −0.68 0 0 121 FGFR2_P460_R −0.39 0 0 122 MME_P388_F 1.09 0 0 123 TNF_P158_F −0.75 0 0 124 MMP2_P303_R 1.22 0 0 125 S100A2_P1186_F −0.87 0 0 126 TRIM29_E189_F −0.87 0 0 127 HLA-DOB_E432_R −0.77 0 0 128 CXCL9_E268_R −0.78 0 0 129 SNURF_P78_F −0.71 0 0 130 FOSL2_E384_R −0.69 0 0 131 AGTR1_P154_F 1.41 0 0 132 PAX6_P50_R 1.42 0 0 133 APOC1_P406_R −0.59 0 0 134 PODXL_P1341_R 1.17 0 0 135 HBII-52_E142_F −0.63 0 0 136 IL1RN_E42_F −0.81 0 0 137 GSTM1_P266_F 0.77 0 0 138 NTSR1_P318_F 1.30 0 0 139 ADCYAP1_P455_R 1.05 0 0 140 SFN_E118_F −0.97 0 0 141 NPR2_P618_F 0.81 0 0 142 ASCL2_E76_R 1.09 0 0 143 DIO3_P674_F 1.03 0 0 144 TRIM29_P261_F −1.30 0 0 145 SLC14A1_E295_F −0.72 0 0 146 SNURF_E256_R −0.55 0 0 147 HBII-52_P563_F −0.81 0 0 148 CDH13_P88_F 0.82 0 0 149 CYP1B1_P212_F −0.31 0 0 150 TAL1_E122_F 1.38 0 0 151 CHGA_E52_F 1.08 0 0 152 TMPRSS4_P552_F −0.57 0 0 153 AIM2_E208_F −0.63 0 0 154 CYP2E1_P416_F −1.11 0 0 155 EYA4_E277_F 1.10 0 0 156 PGR_P790_F −0.62 0 0 157 PROM1_P44_R −0.74 0 0 158 JAK3_E64_F 1.00 0 0 159 MT1A_E13_R 1.08 0 0 160 ZIM3_P718_R −1.08 0 0 161 PDGFRA_P1429_F 1.62 0 0 162 GAS7_E148_F 1.16 0 0 163 LTA_P214_R −0.59 0 0 164 AGXT_P180_F −0.86 0 0 165 GAS7_P622_R 0.93 0 0 166 IL12B_P1453_F −0.47 0 0 167 NEFL_E23_R 0.94 0 0 168 APOC2_P377_F −0.45 0 0 169 OSM_P34_F −0.72 0 0 170 GFI1_E136_F 1.07 0 0 171 LCN2_P141_R −0.88 0 0 172 JAK3_P156_R 0.95 0 0 173 DSG1_P159_R −0.79 0 0 174 HOXC6_P456_R 0.99 0 0 175 MMP7_E59_F −0.50 0 0 176 CREBBP_P712_R −0.74 0 0 177 AGTR1_P41_F 1.63 0 0 178 AATK_E63_R −1.09 0 0 179 SFTPC_E13_F −0.46 0 0 180 FGF6_E294_F −0.50 0 0 181 SNRPN_seq_12_S127_F −0.51 0 0 182 ADCYAP1_E163_R 0.99 0 0 183 GNG7_P903_F −0.52 0 0 184 MYOD1_P50_F 0.79 0 0 185 WEE1_P924_R −0.76 0 0 186 P2RX7_P119_R 0.88 0 0 187 SFTPA1_P421_F −0.60 0 0 188 CTLA4_P1128_F −0.59 0 0 189 MCM2_P260_F −0.36 0 0 190 LCN2_P86_R −0.74 0 0 191 NTRK3_P752_F 1.35 0 0 192 PWCR1_E81_R −1.03 0 0 193 BLK_P14_F −0.60 0 0 194 TMEFF2_P152_R 0.83 0 0 195 GRB10_P496_R 0.65 0 0 196 IGFBP3_P423_R 1.23 0 0 197 ST6GAL1_P528_F 1.19 0 0 198 APBA2_P305_R −0.66 0 0 199 TWIST1_E117_R 1.73 0 0 200 PTPRO_P371_F 0.66 0 0 201 CALCA_P75_F 0.96 0 0 202 CSF1R_E26_F −0.99 0 0 203 TRIP6_E33_F −0.55 0 0 204 MC2R_E455_F −1.29 0 0 205 FGF3_P171_R 1.29 0 0 206 HOXB2_P99_F 0.51 0 0 207 WNT8B_E487_F −0.54 0 0 208 PTK6_E50_F −0.59 0 0 209 PTHR1_E36_R −0.49 0 0 210 VAV1_E9_F −0.77 0 0 211 IL2_P607_R −0.66 0 0 212 ASCL2_P360_F 1.07 0 0 213 MFAP4_P10_R 0.51 0 0 214 ITK_E166_R −0.94 0 0 215 IFNG_P459_R −0.63 0 0 216 NTRK2_P395_R 1.56 0 0 217 GNG7_E310_R −0.41 0 0 218 NTRK3_P636_R 1.04 0 0 219 PTPRH_P255_F −0.90 0 0 220 PGR_P456_R −0.79 0 1.00E−06 221 HTR2A_P853_F 1.11 0 1.00E−06 222 DBC1_E204_F 0.69 0 1.00E−06 223 PLA2G2A_E268_F −0.64 0 1.00E−06 224 PROK2_P390_F 1.80 0 1.00E−06 225 DES_E228_R 0.75 1.00E−06 1.00E−06 226 TNF_P1084_F −0.44 1.00E−06 1.00E−06 227 SFTPB_P689_R −0.46 1.00E−06 1.00E−06 228 TWIST1_P355_R 0.77 1.00E−06 1.00E−06 229 ATP10A_P147_F 0.83 1.00E−06 1.00E−06 230 DHCR24_P652_R −0.35 1.00E−06 1.00E−06 231 BDNF_P259_R 0.62 1.00E−06 1.00E−06 232 BRCA1_P835_R −0.63 1.00E−06 1.00E−06 233 EDNRB_P709_R −1.21 1.00E−06 1.00E−06 234 EPS8_E231_F −0.23 1.00E−06 1.00E−06 235 TRAF4_P372_F −0.32 1.00E−06 1.00E−06 236 MT1A_P49_R 1.79 1.00E−06 1.00E−06 237 NDN_P1110_F −0.69 1.00E−06 1.00E−06 238 AOC3_P890_R −0.50 1.00E−06 1.00E−06 239 PWCR1_P357_F −0.60 1.00E−06 1.00E−06 240 KLK11_P103_R −0.59 1.00E−06 1.00E−06 241 NTRK3_E131_F 1.73 1.00E−06 1.00E−06 242 PI3_E107_F −0.97 1.00E−06 1.00E−06 243 SFRP1_E398_R 1.33 1.00E−06 1.00E−06 244 SFTPA1_E340_R −0.81 1.00E−06 1.00E−06 245 CCND2_P898_R 1.34 1.00E−06 1.00E−06 246 MKRN3_E144_F −1.18 1.00E−06 1.00E−06 247 GDF10_P95_R 0.63 1.00E−06 1.00E−06 248 CD1A_P6_F −0.91 1.00E−06 2.00E−06 249 TJP2_P330_R 1.16 1.00E−06 2.00E−06 250 TPEF_seq_44_S36_F 0.81 1.00E−06 2.00E−06 251 PWCR1_P811_F −0.78 1.00E−06 2.00E−06 252 TWIST1_P44_R 1.32 2.00E−06 2.00E−06 253 ESR1_P151_R 0.87 2.00E−06 2.00E−06 254 GLI2_P295_F −0.61 2.00E−06 2.00E−06 255 EPHB1_E202_R −0.36 2.00E−06 2.00E−06 256 CCL3_P543_R −0.75 2.00E−06 2.00E−06 257 GABRB3_P92_F 0.48 2.00E−06 2.00E−06 258 BLK_P668_R −0.58 2.00E−06 2.00E−06 259 GABRB3_E42_F 0.84 2.00E−06 2.00E−06 260 ITGB4_P517_F −0.31 2.00E−06 2.00E−06 261 SPARC_E50_R 0.41 2.00E−06 2.00E−06 262 EPO_E244_R 1.04 2.00E−06 2.00E−06 263 NPY_P91_F 0.94 2.00E−06 2.00E−06 264 TFF2_P557_R −0.53 2.00E−06 2.00E−06 265 MAS1_P469_R −0.54 2.00E−06 2.00E−06 266 GDF10_E39_F 0.29 2.00E−06 3.00E−06 267 IHH_E186_F 0.95 2.00E−06 3.00E−06 268 CCND2_P887_F 1.50 2.00E−06 3.00E−06 269 PAX6_E129_F 0.88 2.00E−06 3.00E−06 270 CD1A_P414_R −0.71 3.00E−06 3.00E−06 271 IL1RN_P93_R −0.53 3.00E−06 3.00E−06 272 IL12B_E25_F −0.69 3.00E−06 3.00E−06 273 TNFSF10_E53_F −0.55 3.00E−06 3.00E−06 274 MAPK4_E273_R −0.58 3.00E−06 3.00E−06 275 LEFTY2_P561_F 0.44 3.00E−06 3.00E−06 276 EGF_P413_F −0.73 3.00E−06 3.00E−06 277 APC_E117_R 0.67 3.00E−06 3.00E−06 278 OSM_P188_F −0.85 3.00E−06 4.00E−06 279 CSF1R_P73_F −0.40 3.00E−06 4.00E−06 280 LCK_E28_F −0.39 3.00E−06 4.00E−06 281 MEST_P62_R −0.64 4.00E−06 4.00E−06 282 PRSS8_E134_R −0.65 4.00E−06 4.00E−06 283 FRZB_P406_F 1.33 4.00E−06 4.00E−06 284 ISL1_P379_F 0.87 4.00E−06 4.00E−06 285 HS3ST2_P546_F 0.41 4.00E−06 4.00E−06 286 IL18BP_P51_R 0.55 4.00E−06 4.00E−06 287 MEST_E150_F −0.66 4.00E−06 5.00E−06 288 TNFRSF10C_P612_R −0.34 5.00E−06 5.00E−06 289 INS_P248_F −0.65 5.00E−06 5.00E−06 290 SFRP1_P157_F 1.01 5.00E−06 5.00E−06 291 KRT5_E196_R −0.90 6.00E−06 6.00E−06 292 CALCA_P171_F 0.46 6.00E−06 6.00E−06 293 TRPM5_E87_F −0.74 6.00E−06 6.00E−06 294 HLA-DQA2_E93_F −0.39 6.00E−06 6.00E−06 295 RUNX3_P247_F −0.59 6.00E−06 6.00E−06 296 RASSF1_P244_F 1.61 6.00E−06 6.00E−06 297 AGXT_E115_R −0.83 6.00E−06 6.00E−06 298 EPHA5_E158_R 0.96 6.00E−06 6.00E−06 299 MYB_P673_R −0.20 7.00E−06 7.00E−06 300 AFP_P824_F −0.54 7.00E−06 7.00E−06 301 RHOH_P953_R −0.47 7.00E−06 7.00E−06 302 MBD2_P233_F −0.40 7.00E−06 7.00E−06 303 ZNFN1A1_E102_F −0.53 7.00E−06 7.00E−06 304 HOXA11_P92_R 0.93 8.00E−06 8.00E−06 305 TDGF1_P428_R −0.37 8.00E−06 8.00E−06 306 PADI4_E24_F −0.70 8.00E−06 8.00E−06 307 DSP_P36_F −0.32 9.00E−06 9.00E−06 308 ALK_P28_F −0.57 9.00E−06 9.00E−06 309 NBL1_E205_R −0.59 9.00E−06 9.00E−06 310 FGF3_E198_R 1.33 9.00E−06 9.00E−06 311 OPCML_E219_R 0.91 9.00E−06 9.00E−06 312 MKRN3_P108_F −0.75 1.00E−05 9.00E−06 313 FLT4_P180_R 0.96 1.00E−05 9.00E−06 314 GALR1_P80_F 0.65 1.00E−05 1.00E−05 315 FGF8_P473_F 0.79 1.00E−05 1.00E−05 316 HTR1B_P107_F 0.33 1.10E−05 1.00E−05 317 DSC2_P407_R −0.64 1.10E−05 1.00E−05 318 PMP22_P975_F −0.65 1.10E−05 1.00E−05 319 B3GALT5_E246_R −0.53 1.10E−05 1.00E−05 320 ZIM2_P22_F 0.38 1.10E−05 1.00E−05 321 FGFR4_P610_F −0.47 1.10E−05 1.00E−05 322 CDKN1C_P626_F 0.62 1.20E−05 1.10E−05 323 HIC2_P498_F 1.01 1.20E−05 1.10E−05 324 RASSF1_E116_F 1.40 1.20E−05 1.10E−05 325 TDGF1_E53_R −0.41 1.20E−05 1.20E−05 326 MMP8_E89_R −0.80 1.30E−05 1.20E−05 327 TBX1_P885_R 0.87 1.30E−05 1.20E−05 328 HPSE_P29_F −0.25 1.30E−05 1.20E−05 329 MYH11_P22_F 1.11 1.30E−05 1.20E−05 330 KDR_P445_R 1.13 1.40E−05 1.30E−05 331 DSG1_E292_F −0.39 1.50E−05 1.30E−05 332 HOXB13_P17_R 0.69 1.50E−05 1.40E−05 333 TNFSF8_E258_R −0.60 1.60E−05 1.40E−05 334 SPDEF_E116_R −0.47 1.60E−05 1.40E−05 335 ABCB4_E429_F −0.40 1.70E−05 1.50E−05 336 FLI1_E29_F 0.64 1.70E−05 1.50E−05 337 EDNRB_P148_R −0.75 1.70E−05 1.60E−05 338 HLA-DOB_P357_R −0.32 1.80E−05 1.60E−05 339 HSPA2_P162_R −0.48 1.90E−05 1.70E−05 340 ZIM3_P451_R −0.69 1.90E−05 1.70E−05 341 EGF_E339_F −0.69 1.90E−05 1.70E−05 342 PDGFRB_E195_R 0.65 2.00E−05 1.70E−05 343 MMP1_P460_F −0.57 2.00E−05 1.70E−05 344 ABCB4_P51_F −0.46 2.00E−05 1.70E−05 345 TCF4_P317_F 0.82 2.00E−05 1.80E−05 346 NCL_P1102_F −0.72 2.10E−05 1.80E−05 347 MAS1_P657_R −0.47 2.20E−05 1.90E−05 348 SMO_P455_R 1.00 2.20E−05 1.90E−05 349 GFAP_P56_R −0.44 2.30E−05 2.00E−05 350 TDG_E129_F −0.53 2.60E−05 2.20E−05 351 MMP1_P397_R −0.47 2.70E−05 2.30E−05 352 CFTR_P372_R 0.51 2.70E−05 2.30E−05 353 GUCY2D_E419_R 1.13 2.70E−05 2.30E−05 354 PTHR1_P258_F −0.40 2.80E−05 2.30E−05 355 MMP2_P197_F 0.78 2.80E−05 2.30E−05 356 TFDP1_P543_R −0.29 2.80E−05 2.40E−05 357 IFNG_P188_F −0.64 2.90E−05 2.50E−05 358 CDK10_P199_R −0.35 2.90E−05 2.50E−05 359 FES_P223_R 0.86 3.00E−05 2.50E−05 360 TES_P182_F −0.33 3.00E−05 2.50E−05 361 EYA4_P508_F 0.51 3.00E−05 2.50E−05 362 IGFBP2_P306_F 0.92 3.00E−05 2.50E−05 363 AFF3_P808_F −0.84 3.00E−05 2.50E−05 364 MLH3_P25_F −0.22 3.00E−05 2.50E−05 365 FRK_P258_F −0.57 3.10E−05 2.60E−05 366 WNT2_P217_F 0.78 3.20E−05 2.60E−05 367 RIPK3_P124_F −0.48 3.20E−05 2.60E−05 368 NGFR_P355_F 0.51 3.20E−05 2.60E−05 369 SRC_P164_F −0.43 3.50E−05 2.80E−05 370 PRDM2_P1340_R −0.42 3.70E−05 3.00E−05 371 p16_seq_47_S188_R 1.53 3.80E−05 3.10E−05 372 KIAA0125_E29_F −0.60 3.90E−05 3.10E−05 373 IL8_P83_F −0.60 4.10E−05 3.30E−05 374 ZNF215_P129_R 0.71 4.60E−05 3.70E−05 375 H19_P1411_R −0.57 4.70E−05 3.70E−05 376 RAN_P581_R −0.48 4.80E−05 3.80E−05 377 IL10_P85_F −0.61 5.00E−05 4.00E−05 378 MYH11_P236_R 1.12 5.10E−05 4.10E−05 379 NOS2A_P288_R −0.49 5.40E−05 4.30E−05 380 SERPINA5_E69_F −0.42 5.50E−05 4.30E−05 381 TAL1_P817_F 0.51 5.60E−05 4.40E−05 382 RUNX3_P393_R −0.50 5.60E−05 4.40E−05 383 THBS2_E129_F 0.91 5.80E−05 4.50E−05 384 E2F5_P516_R −0.44 5.80E−05 4.60E−05 385 GPATC3_P410_R −0.57 6.00E−05 4.60E−05 386 PEG3_E496_F 0.30 6.00E−05 4.60E−05 387 SNRPN_seq_18_S99_F −0.33 6.10E−05 4.80E−05 388 FGFR1_P204_F 0.62 6.20E−05 4.80E−05 389 TERT_E20_F 0.71 6.40E−05 4.90E−05 390 GATA6_P726_F 0.83 6.60E−05 5.10E−05 391 GADD45A_P737_R −0.36 6.70E−05 5.10E−05 392 ZIM2_E110_F 0.28 6.80E−05 5.20E−05 393 NRG1_P558_R 0.51 7.30E−05 5.50E−05 394 HOXA5_E187_F 0.57 7.30E−05 5.50E−05 395 IAPP_E280_F −0.50 7.30E−05 5.50E−05 396 SPP1_E140_R −0.44 7.80E−05 5.90E−05 397 CDH1_P52_R 0.33 7.80E−05 5.90E−05 398 GLI2_E90_F −0.73 7.90E−05 6.00E−05 399 ABCC2_P88_F −0.70 8.00E−05 6.00E−05 400 MAGEL2_P170_R −0.62 8.10E−05 6.10E−05 401 PGR_E183_R −0.52 8.30E−05 6.20E−05 402 SNRPN_P230_R −0.41 8.30E−05 6.20E−05 403 DDR1_E23_R −0.29 8.30E−05 6.20E−05 404 MAGEL2_E166_R −0.71 8.40E−05 6.30E−05 405 USP29_P205_R −0.36 8.60E−05 6.30E−05 406 RIPK2_E123_F −0.19 8.60E−05 6.40E−05 407 USP29_P282_R −0.31 8.80E−05 6.50E−05 408 SEPT5_P441_F 0.53 9.50E−05 7.00E−05 409 DDB2_P407_F −0.22 0.000104 7.60E−05 410 ISL1_P554_F 0.66 0.000106 7.70E−05 411 SPI1_E205_F −0.29 0.000108 7.90E−05 412 COL1A2_E299_F 1.12 0.000109 7.90E−05 413 EVI2A_P94_R −0.69 0.000109 7.90E−05 414 DES_P1006_R −0.42 0.000109 7.90E−05 415 TGFB2_E226_R 0.68 0.000109 7.90E−05 416 CDH11_P203_R 0.71 0.000115 8.30E−05 417 BDNF_E19_R 0.50 0.000115 8.30E−05 418 FGF9_P1404_F −0.19 0.000117 8.40E−05 419 PTHLH_P15_R −0.51 0.000124 8.90E−05 420 BCL2A1_P1127_R −0.61 0.000125 9.00E−05 421 DNMT1_P100_R −0.26 0.000126 9.00E−05 422 DNAJC15_E26_R 0.48 0.000132 9.40E−05 423 MALT1_P406_R −0.27 0.000135 9.60E−05 424 FGR_P39_F −0.51 0.000137 9.70E−05 425 HBII-52_P659_F −0.69 0.000142 1.00E−04 426 EPM2A_P113_F −0.30 0.000147 0.000103 427 PPARG_P693_F −0.39 0.000151 0.000106 428 ETS2_P684_F −0.28 0.000151 0.000106 429 ZP3_P220_F −0.48 0.000152 0.000106 430 NTRK2_P10_F 1.18 0.000153 0.000107 431 FGF12_P210_R 0.98 0.000154 0.000107 432 MUSK_P308_F −0.41 0.000157 0.000109 433 HOXB2_P488_R 0.54 0.000163 0.000113 434 IRAK3_P185_F 0.42 0.000164 0.000113 435 COL1A2_P48_R 1.05 0.00017 0.000117 436 ELL_P693_F −0.38 0.000171 0.000118 437 MFAP4_P197_F 0.52 0.000174 0.000119 438 SIN3B_P514_R −0.51 0.000193 0.000132 439 APC_P280_R 0.91 0.000193 0.000132 440 SEZ6L_P249_F 0.92 0.000201 0.000137 441 LMO2_E148_F −0.74 0.000204 0.000139 442 LTA_E28_R −0.66 0.000208 0.000141 443 MAPK10_E26_F −0.63 0.000208 0.000141 444 SPDEF_P6_R −0.37 0.00023 0.000155 445 FGFR2_P266_R −0.22 0.00024 0.000161 446 MMP9_P189_F −0.48 0.00024 0.000161 447 KRT13_P676_F 0.37 0.000241 0.000162 448 IL12B_P392_R −0.69 0.000249 0.000167 449 TRPM5_P979_F −0.55 0.000253 0.000169 450 GJB2_P931_R 0.49 0.000257 0.000171 451 MYLK_E132_R −0.26 0.000263 0.000175 452 ARHGAP9_P260_F −0.50 0.000265 0.000176 453 MMP9_E88_R −0.48 0.000287 0.00019 454 HOXC6_P585_R 0.47 0.000288 0.00019 455 PXN_P308_F 0.26 0.000296 0.000195 456 IMPACT_P186_F 0.25 0.000327 0.000215 457 TFF1_P180_R −0.48 0.000328 0.000215 458 COL1A2_P407_R 0.36 0.000329 0.000216 459 ZIM3_E203_F −0.50 0.000332 0.000217 460 THPO_E483_F −0.59 0.000333 0.000217 461 TMEFF2_E94_R 0.74 0.000333 0.000217 462 ZNF264_P397_F 0.34 0.00034 0.000221 463 CSF3R_P8_F 0.50 0.000346 0.000224 464 SLC22A3_E122_R 0.66 0.000369 0.000239 465 TESK2_P252_R 0.21 0.000375 0.000242 466 SCGB3A1_E55_R 0.61 0.000377 0.000243 467 THBS1_P500_F −0.21 0.000403 0.000259 468 RET_seq_53_S374_F 0.89 0.000411 0.000263 469 IL18BP_E285_F 0.31 0.000412 0.000263 470 MMP3_P16_R −0.69 0.000425 0.000271 471 IRAK3_P13_F 1.29 0.000426 0.000271 472 PLAGL1_P334_F −0.34 0.000432 0.000275 473 FLT3_P302_F 0.80 0.000443 0.00028 474 CCKAR_P270_F −0.48 0.000443 0.00028 475 SMAD2_P848_R −0.24 0.000448 0.000283 476 HHIP_P578_R 0.40 0.000451 0.000284 477 MPO_E302_R −0.34 0.000463 0.000291 478 FANCA_P1006_R −0.64 0.000492 0.000309 479 MAP3K1_P7_F −0.26 0.000493 0.000309 480 LMO2_P794_R −0.61 0.000516 0.000322 481 TNFRSF1B_E5_F 0.42 0.00052 0.000325 482 PADI4_P1011_R −0.37 0.000521 0.000325 483 TRIP6_P1090_F −0.50 0.000524 0.000325 484 CCKBR_P480_F 0.88 0.000524 0.000325 485 SMO_E57_F 0.75 0.000528 0.000327 486 DNAJC15_P65_F −0.55 0.000537 0.000332 487 IGF2_P36_R 0.37 0.00055 0.000339 488 SERPINB2_P939_F −0.53 0.000558 0.000343 489 IRAK3_E130_F 1.07 0.000593 0.000364 490 LIF_P383_R −0.30 0.000606 0.000371 491 ABCB4_P892_F −0.62 0.000612 0.000374 492 SPI1_P48_F −0.68 0.000621 0.000379 493 WNT10B_P823_R 0.51 0.000626 0.000381 494 SOD3_P225_F −0.35 0.000631 0.000383 495 ACVR1_P983_F −0.46 0.000633 0.000384 496 RAD54B_P227_F −0.25 0.000634 0.000384 497 ZNFN1A1_P179_F −0.56 0.000648 0.000391 498 PLG_P370_F −0.30 0.00065 0.000391 499 HTR2A_E10_R −0.48 0.00065 0.000391 500 HLA-DPB1_P540_F −0.47 0.000654 0.000393 501 TMEFF2_P210_R 0.42 0.000659 0.000395 502 TUSC3_E29_R 0.42 0.000684 0.000409 503 CCND1_E280_R −0.19 0.000685 0.000409 504 SEZ6L_P299_F 0.74 0.00072 0.000429 505 HCK_P46_R 0.67 0.000769 0.000457 506 THBS1_E207_R 0.29 0.000776 0.00046 507 HDAC11_P556_F 0.12 0.00079 0.000467 508 TIMP3_P1114_R −0.40 0.000798 0.000471 509 DSC2_E90_F −0.36 0.000813 0.000479 510 ABCC2_E16_R −0.54 0.000819 0.000482 511 ACVR1C_P115_R −0.21 0.000881 0.000517 512 TES_E172_F −0.28 0.000901 0.000528 513 CFTR_P115_F 0.79 0.00091 0.000532 514 IL13_E75_R −0.37 0.000912 0.000532 515 PROK2_E0_F 0.42 0.000918 0.000535 516 PTCH2_E173_F −0.25 0.000946 0.00055 517 S100A12_P1221_R −0.38 0.000967 0.000561 518 VAMP8_P241_F −0.35 0.000978 0.000566 519 KLK11_P1290_F −0.37 0.000992 0.000574 520 SHB_P691_R −0.27 0.001004 0.000579 521 PCDH1_E22_F 0.11 0.001009 0.000581 522 DLC1_P88_R −0.35 0.001019 0.000586 523 PARP1_P610_R −0.37 0.001025 0.000589 524 FGF12_E61_R 0.60 0.001056 0.000605 525 CTLA4_E176_R −0.39 0.001072 0.000612 526 FGF7_P44_F −0.50 0.001073 0.000612 527 IGF1R_E186_R 0.42 0.001076 0.000612 528 POMC_P53_F 0.91 0.001077 0.000612 529 MMP10_E136_R −0.36 0.001116 0.000633 530 ARHGAP9_P518_R −0.36 0.001123 0.000636 531 FGF1_E5_F −0.39 0.001146 0.000648 532 DAB2_P468_F 1.17 0.001156 0.000652 533 BMP2_E48_R 0.49 0.00116 0.000653 534 CTSD_P726_F −0.32 0.001165 0.000655 535 HBII-13_E48_F −0.41 0.001194 0.000669 536 MLLT3_E93_R 0.12 0.001195 0.000669 537 TNFRSF10C_P7_F 0.60 0.001232 0.000688 538 LYN_E353_F −0.24 0.00124 0.000692 539 CRIP1_P874_R 0.46 0.001252 0.000697 540 RAD50_P191_F −0.37 0.001311 0.000729 541 ACTG2_P455_R −0.27 0.001317 0.000731 542 PALM2-AKAP2_P420_R 0.39 0.001331 0.000737 543 FGF1_P357_R −0.42 0.001387 0.000767 544 MSH3_E3_F −0.46 0.001397 0.000771 545 EPHA5_P66_F 0.31 0.0014 0.000771 546 JAG1_P66_F −0.22 0.001423 0.000782 547 TP73_P945_F 0.49 0.001448 0.000795 548 CEACAM1_P44_R −0.35 0.001472 0.000806 549 HLA-DRA_P77_R −0.36 0.001485 0.000812 550 PRKCDBP_E206_F 0.98 0.001528 0.000832 551 ERCC6_P698_R −0.17 0.001528 0.000832 552 GABRA5_E44_R −0.30 0.001536 0.000835 553 TMEFF1_P626_R −0.24 0.00154 0.000836 554 WNT1_P79_R 0.48 0.001545 0.000837 555 GPX1_P194_F 0.49 0.001559 0.000842 556 UGT1A7_P751_R −0.28 0.00156 0.000842 557 NOTCH1_E452_R 0.21 0.001562 0.000842 558 PITX2_P183_R 0.33 0.001596 0.000859 559 EGF_P242_R −0.40 0.001637 0.000879 560 MCM6_E136_F −0.21 0.001663 0.000891 561 CHD2_P667_F −0.30 0.001683 0.000901 562 NKX3-1_P871_R −0.49 0.001712 0.000914 563 FGF5_E16_F 0.56 0.001725 0.00092 564 DAB2_P35_F 0.89 0.001735 0.000923 565 CPA4_P1265_R −0.19 0.001751 0.00093 566 ERCC1_P354_F 0.13 0.001779 0.000943 567 WNT8B_P216_R −0.24 0.001878 0.000994 568 MMP2_E21_R 0.55 0.001883 0.000995 569 EPHA3_P106_R 0.56 0.001901 0.001003 570 AATK_P709_R −0.40 0.001933 0.001018 571 SEMA3C_P642_F −0.32 0.002005 0.001054 572 PHLDA2_E159_R 0.14 0.002031 0.001066 573 MAF_P826_R 0.81 0.002046 0.001072 574 PYCARD_E87_F 1.08 0.002076 0.001086 575 CYP2E1_E53_R −0.44 0.002098 0.001095 576 ABCG2_P310_R 1.31 0.002107 0.001098 577 WNT10B_P993_F 0.40 0.002119 0.001101 578 LAT_E46_F −0.37 0.00212 0.001101 579 ASCL2_P609_R 0.39 0.002186 0.001133 580 JAK3_P1075_R −0.38 0.002218 0.001147 581 IGSF4C_E65_F −0.22 0.00222 0.001147 582 TNFRSF10D_P70_F 0.68 0.002236 0.001154 583 SHH_E328_F 0.34 0.002257 0.001162 584 KRAS_E82_F −0.22 0.002278 0.00117 585 ZNF215_P71_R 0.29 0.00228 0.00117 586 IGF2_P1036_R 0.25 0.00235 0.001204 587 EGR4_E70_F −0.18 0.00237 0.001212 588 B3GALT5_P330_F −0.27 0.002378 0.001214 589 FLI1_P620_R 0.48 0.002432 0.00124 590 SLC22A2_E271_R −0.62 0.002446 0.001245 591 HGF_P1293_R −0.65 0.002471 0.001255 592 TM7SF3_P1068_R −0.53 0.002522 0.001279 593 CCKBR_P361_R 0.34 0.002563 0.001297 594 EPHB1_P503_F 0.54 0.002588 0.001308 595 PDGFA_P78_F −0.17 0.002603 0.001312 596 HIC2_P528_R 0.44 0.002605 0.001312 597 ETV1_P235_F 0.59 0.002627 0.001321 598 NPY_E31_R 0.30 0.002638 0.001324 599 MAPK12_P416_F 0.53 0.002649 0.001327 600 EVI2A_E420_F −0.35 0.002652 0.001327 601 GSTM2_E153_F 0.57 0.00276 0.001378 602 TNFRSF10C_E109_F 0.74 0.002793 0.001393 603 CREB1_P819_F −0.40 0.0028 0.001394 604 LIG3_P622_R −0.34 0.002914 0.001449 605 EPHB4_E476_R −0.23 0.002948 0.001462 606 SLC5A8_P38_R 0.36 0.002951 0.001462 607 MMP19_P306_F −0.40 0.002972 0.00147 608 FASTK_P257_F −0.22 0.002998 0.00148 609 FES_E34_R 0.45 0.003052 0.001505 610 ALPL_P433_F 0.30 0.003132 0.001541 611 RET_P717_F 0.29 0.003244 0.001594 612 MAP3K1_E81_F −0.29 0.003287 0.001612 613 LYN_P241_F 0.23 0.003391 0.001661 614 EPS8_P437_F −0.21 0.003414 0.00167 615 S100A2_E36_R −0.34 0.003438 0.001678 616 RASGRF1_E16_F 0.47 0.003459 0.001686 617 DAPK1_P345_R 0.36 0.003534 0.00172 618 RIPK3_P24_F −0.38 0.003628 0.001762 619 NES_P239_R 0.40 0.003855 0.00187 620 PAX6_P1121_F 0.62 0.00389 0.001884 621 COL4A3_E205_R 0.42 0.003961 0.001915 622 CCNA1_E7_F 0.73 0.003977 0.00192 623 EPHA1_E46_R −0.49 0.004013 0.001934 624 APBA2_P227_F −0.44 0.004082 0.001964 625 FGF7_P610_F −0.25 0.004143 0.00199 626 POMC_E254_F 0.26 0.004156 0.00199 627 CD9_P585_R −0.37 0.004156 0.00199 628 RHOH_P121_F −0.47 0.004166 0.001992 629 CDC25B_P11_R 1.14 0.004195 0.002002 630 ZP3_E90_F 0.76 0.004202 0.002003 631 IL3_P556_F −0.23 0.004233 0.002014 632 MCC_P196_R 0.14 0.004247 0.002017 633 NCL_P840_R −0.19 0.004299 0.002039 634 PSCA_P135_F −0.28 0.004314 0.002043 635 RBP1_E158_F 0.93 0.004376 0.002069 636 FABP3_E113_F 0.45 0.004423 0.002088 637 DIO3_P90_F 0.18 0.00445 0.002097 638 ADAMTS12_P250_R 0.74 0.004465 0.002101 639 UGT1A1_P315_R −0.29 0.004533 0.002128 640 TFF2_P178_F −0.36 0.004536 0.002128 641 HDAC9_E38_F 0.54 0.004567 0.002139 642 ALOX12_E85_R −0.46 0.004585 0.002144 643 ASCL1_P747_F 0.28 0.004643 0.002168 644 UGT1A1_E11_F −0.45 0.004771 0.002224 645 TYK2_P494_F −0.28 0.004867 0.002265 646 C4B_P191_F −0.36 0.004898 0.002274 647 EFNB3_E17_R 0.13 0.0049 0.002274 648 HLA-DOB_P1114_R −0.29 0.004911 0.002275 649 NRG1_E74_F 0.24 0.004932 0.002282 650 CDH17_P532_F −0.26 0.004941 0.002282 651 CDKN2B_E220_F 0.14 0.005065 0.002334 652 PTPRO_E56_F 0.92 0.005069 0.002334 653 CHFR_P635_R 0.40 0.005146 0.002366 654 TGFBR3_P429_F 0.39 0.005172 0.002372 655 TUBB3_P364_F 0.11 0.005175 0.002372 656 CD40_E58_R 0.62 0.005263 0.002409 657 FLT1_E444_F 0.58 0.005304 0.002424 658 CRIP1_P274_F −0.22 0.005319 0.002427 659 EPHB3_E0_F −0.33 0.005381 0.002452 660 THY1_P20_R −0.16 0.005698 0.002592 661 SNURF_P2_R −0.21 0.005729 0.002602 662 IL4_P262_R −0.23 0.005811 0.002636 663 PMP22_P1254_F −0.23 0.005954 0.002697 664 TIMP3_seq_7_S38_F 0.54 0.006101 0.002755 665 GSTM2_P109_R 0.58 0.006102 0.002755 666 PTCH2_P568_R 0.24 0.006579 0.002963 667 HOXA5_P479_F 0.33 0.006581 0.002963 668 MAPK9_P1175_F −0.39 0.006629 0.00298 669 KDR_E79_F 0.49 0.006779 0.003043 670 RET_seq_54_S260_F 0.62 0.006835 0.003063 671 PECAM1_E32_R 0.33 0.006848 0.003065 672 PDGFRB_P343_F 0.68 0.006889 0.003077 673 NOTCH1_P1198_F 0.23 0.006897 0.003077 674 CDH17_E31_F −0.47 0.00697 0.003105 675 ELK3_P514_F 0.42 0.007191 0.003199 676 FGF6_P139_R −0.42 0.007281 0.003234 677 ROR1_P6_F 0.28 0.007355 0.003262 678 GNAS_P86_F −0.26 0.007434 0.003292 679 EPHB2_P165_R −0.28 0.007461 0.003299 680 RAP1A_P285_R −0.22 0.007518 0.00332 681 EPHA8_P456_R −0.32 0.00754 0.003324 682 CTSL_P81_F 0.52 0.007574 0.003335 683 KIT_P405_F 0.47 0.00764 0.003359 684 STAT5A_P704_R −0.42 0.00765 0.003359 685 OPCML_P71_F 0.28 0.00774 0.003393 686 TRPM5_P721_F −0.35 0.007892 0.003454 687 GLI3_E148_R −0.35 0.008373 0.00366 688 IL1A_E113_R −0.24 0.008414 0.003672 689 CD40_P372_R 0.48 0.008466 0.00369 690 SERPINE1_P519_F 0.34 0.008532 0.003713 691 TGFB1_P833_R −0.43 0.008552 0.003716 692 KRT5_P308_F −0.27 0.008597 0.00373 693 SPI1_P929_F −0.30 0.008724 0.00378 694 PURA_P928_R 0.67 0.008889 0.003846 695 HLA-F_E402_F 1.19 0.00896 0.003871 696 NGFR_E328_F 0.40 0.009003 0.003884 697 ABO_P312_F 0.33 0.009046 0.003897 698 ITGA6_P718_R −0.40 0.009142 0.003933 699 LRRK1_P39_F −0.19 0.009165 0.003937 700 INSR_P1063_R 0.34 0.009426 0.004044 701 BMP6_P163_F 0.54 0.009492 0.004066 702 SLC22A2_P109_F −0.28 0.009558 0.004089 703 DIRAS3_E55_R −0.35 0.009641 0.004118 704 MGMT_P272_R 0.26 0.00967 0.004125 705 NTSR1_E109_F 0.45 0.009851 0.004196 706 ASB4_P391_F −0.37 0.009935 0.004226 707 TNFRSF10D_E27_F 0.72 0.009953 0.004227 708 IGF2_E134_R 0.41 0.010033 0.004255 709 MATK_P64_F 0.34 0.010174 0.004309 710 TFAP2C_P765_F 0.64 0.010193 0.004311 711 IRF7_P277_R 0.73 0.010334 0.004365 712 FGF5_P238_R 0.67 0.010528 0.00444 713 ASCL1_E24_F 0.46 0.010576 0.004452 714 GNAS_E58_F −0.37 0.010586 0.004452 715 COL18A1_P365_R 0.35 0.010763 0.004511 716 TNFRSF10A_P171_F −0.28 0.010766 0.004511 717 LRRC32_E157_F −0.27 0.01077 0.004511 718 HFE_E273_R 1.06 0.010942 0.004577 719 LEFTY2_P719_F 0.26 0.010967 0.00458 720 HGF_E102_R 0.42 0.011004 0.00459 721 MMP3_P55_F −0.26 0.011125 0.004634 722 APBA1_E99_R 0.34 0.011459 0.004766 723 HLA-DRA_P132_R 0.36 0.011485 0.00477 724 FGF8_E183_F 0.31 0.011633 0.004814 725 RBP1_P150_F 0.78 0.011637 0.004814 726 APP_E8_F 0.14 0.011639 0.004814 727 H19_P541_F −0.39 0.011927 0.004927 728 ID1_P659_R 0.22 0.01199 0.004946 729 TJP2_P518_F 0.43 0.01203 0.004955 730 SMAD2_P708_R 0.11 0.01206 0.004961 731 IL1B_P582_R −0.32 0.01223 0.005024 732 IGSF4_P86_R 0.28 0.012321 0.005055 733 TBX1_P520_F −0.27 0.012576 0.005146 734 CDH17_P376_F −0.42 0.012593 0.005146 735 TNFSF8_P184_F −0.29 0.012595 0.005146 736 FER_E119_F −0.23 0.012708 0.005185 737 PLXDC2_E337_F 0.43 0.012842 0.005233 738 NGFB_E353_F 0.28 0.012983 0.005281 739 DCN_P1320_R −0.56 0.012995 0.005281 740 EFNA1_P7_F 0.12 0.013116 0.005323 741 DMP1_P134_F −0.29 0.0133 0.00539 742 ALOX12_P223_R −0.38 0.013537 0.005479 743 MSH3_P13_R −0.24 0.013577 0.005488 744 SEPT5_P464_R 0.30 0.013657 0.005513 745 PDGFB_P719_F −0.29 0.013738 0.005538 746 MGMT_P281_F 0.67 0.01379 0.005551 747 CCNA1_P216_F 0.39 0.014115 0.005675 748 IGFBP3_P1035_F 0.77 0.014227 0.005712 749 MMP19_E274_R −0.28 0.014371 0.005758 750 EPHA1_P119_R 0.13 0.014381 0.005758 751 MPL_P62_F −0.34 0.014737 0.005893 752 PEG10_P978_R 0.28 0.014966 0.005969 753 GPR116_E328_R −0.42 0.014966 0.005969 754 TSP50_P137_F 0.36 0.01502 0.005982 755 CSPG2_E38_F 0.29 0.015051 0.005987 756 JUNB_P1149_R 0.11 0.015405 0.006119 757 CARD15_P665_F −0.30 0.016222 0.006436 758 FLT1_P615_R 0.41 0.016324 0.006467 759 RARRES1_E235_F 0.70 0.016438 0.006504 760 PLSCR3_P751_R −0.18 0.016796 0.00663 761 IL6_P611_F −0.46 0.0168 0.00663 762 COL6A1_P425_F −0.14 0.016957 0.006683 763 MEG3_E91_F 0.22 0.017248 0.006789 764 GRB7_P160_R −0.22 0.017413 0.006845 765 PYCARD_P393_F 0.22 0.017478 0.006862 766 MME_E29_F 0.44 0.017956 0.00704 767 CDH11_P354_R 0.27 0.01803 0.00706 768 GJB2_P791_R 0.33 0.018132 0.00709 769 MAPK12_E165_R 0.46 0.01821 0.007112 770 GAS1_P754_R 0.60 0.018243 0.007115 771 DHCR24_P406_R −0.14 0.018445 0.007185 772 PGF_P320_F 0.27 0.018997 0.00739 773 ITGB1_P451_F −0.11 0.019078 0.007412 774 GPX1_E46_R 0.29 0.019196 0.00743 775 APC_P14_F 0.44 0.019199 0.00743 776 IL17RB_P788_R 0.71 0.019199 0.00743 777 CSPG2_P82_R 0.41 0.019233 0.007434 778 CDH11_E102_R 0.35 0.019527 0.007538 779 LRRC32_P865_R 0.39 0.019566 0.007543 780 GFAP_P1214_F −0.17 0.019767 0.007611 781 GAS1_E22_F 0.55 0.019803 0.007615 782 IGFBP5_P9_R 0.34 0.020162 0.007743 783 LY6G6E_P45_R −0.37 0.020225 0.007758 784 TFPI2_P9_F 0.54 0.020363 0.0078 785 DLL1_P386_F 0.90 0.020488 0.007838 786 YES1_P216_F −0.19 0.020681 0.007902 787 KIT_P367_R 0.48 0.021303 0.008129 788 BMPR2_E435_F 0.12 0.021477 0.008183 789 BMP3_P56_R 0.15 0.021499 0.008183 790 IHH_P246_R 0.24 0.021722 0.008258 791 KCNK4_E3_F 0.28 0.021772 0.008267 792 MXI1_P1269_F −0.27 0.021846 0.008284 793 GLI3_P453_R 0.21 0.022357 0.008467 794 DAB2IP_P9_F 0.38 0.022711 0.008591 795 MAF_E77_R −0.16 0.022809 0.008617 796 FER_P581_F −0.28 0.023416 0.00883 797 ITGA6_P298_R −0.18 0.023432 0.00883 798 TFAP2C_E260_F 0.26 0.023919 0.009002 799 SLC5A8_E60_R 0.24 0.024027 0.009031 800 SLC22A3_P528_F 0.23 0.024829 0.009321 801 PTHR1_P170_R −0.15 0.024961 0.009359 802 HBII-13_P991_R −0.21 0.025018 0.009366 803 KRAS_P651_F 0.14 0.025041 0.009366 804 FZD9_E458_F 0.32 0.025087 0.009371 805 FRK_P36_F −0.29 0.025376 0.009468 806 IMPACT_P234_R 0.24 0.025558 0.009524 807 ZMYND10_E77_R −0.31 0.025804 0.009603 808 PLAGL1_E68_R −0.22 0.026242 0.009754 809 SYK_P584_F −0.25 0.026623 0.009884 810 TMEM63A_E63_F 0.18 0.02669 0.009896 811 PDE1B_P263_R 0.47 0.02699 0.009995 812 FLT1_P302_F 0.27 0.027166 0.010022 813 PTCH2_P37_F 0.51 0.027182 0.010022 814 EPHB6_E342_F 0.32 0.027183 0.010022 815 ESR1_E298_R 0.49 0.027196 0.010022 816 ST6GAL1_P164_R −0.25 0.027515 0.010116 817 FGF9_P862_R 0.11 0.027524 0.010116 818 F2R_P88_F 0.35 0.027551 0.010116 819 AATK_P519_R −0.33 0.027672 0.010148 820 DDR2_E331_F 0.17 0.027976 0.010247 821 LTB4R_E64_R 0.28 0.028847 0.010553 822 HHIP_E94_F 0.24 0.029291 0.010703 823 TIAM1_P188_R 0.54 0.029756 0.010847 824 EPM2A_P64_R 0.08 0.029759 0.010847 825 PTPNS1_P301_R 0.31 0.029805 0.010851 826 CSF2_E248_R −0.27 0.030167 0.010963 827 RAB32_E314_R 0.46 0.030185 0.010963 828 CEBPA_P1163_R 0.33 0.030256 0.010975 829 MYCN_E77_R 0.41 0.030598 0.011086 830 KLF5_E190_R −0.11 0.030846 0.011162 831 ERCC3_P1210_R −0.33 0.031377 0.011341 832 LIF_E208_F 0.55 0.031721 0.011451 833 TNFRSF10A_P91_F −0.20 0.032152 0.011593 834 CDKN1B_P1161_F 0.51 0.032854 0.011832 835 EGFR_E295_R 0.17 0.033261 0.011964 836 PDGFB_E25_R −0.17 0.033456 0.01202 837 BMP6_P398_F 0.65 0.033816 0.012135 838 EPHA7_E6_F 0.31 0.03448 0.012358 839 CCND3_P435_F 0.13 0.03455 0.012368 840 ETV1_P515_F 0.30 0.034623 0.01238 841 WRN_P969_F −0.35 0.034847 0.012445 842 TIAM1_P117_F 0.43 0.035069 0.01251 843 CYP1A1_P382_F 0.17 0.035318 0.012584 844 INS_P804_R −0.51 0.036383 0.012948 845 SRC_E100_R −0.24 0.037053 0.013171 846 EPHA7_P205_R 0.26 0.037751 0.013403 847 CD81_P211_F 0.27 0.037917 0.013446 848 PLXDC1_P236_F 0.32 0.037961 0.013446 849 EFNB3_P442_R −0.16 0.038741 0.013706 850 SLC22A18_P472_R 0.12 0.039068 0.013805 851 C20orf47_P225_R 0.12 0.040231 0.0142 852 PHLDA2_P622_F −0.20 0.040279 0.0142 853 CSF3R_P472_F −0.29 0.040329 0.014201 854 CSF3_E242_R 0.25 0.040378 0.014201 855 HLA-DPA1_P205_R −0.22 0.040677 0.01429 856 IGFBP3_E65_R 0.46 0.040912 0.014356 857 ERBB4_P541_F 0.43 0.041104 0.014406 858 ACTG2_E98_R −0.24 0.041329 0.014468 859 RUNX1T1_E145_R 0.30 0.041509 0.014514 860 ETS1_E253_R −0.14 0.04156 0.014515 861 DLC1_E276_F −0.27 0.041994 0.01465 862 ER_seq_a1_S60_F 0.24 0.042411 0.014778 863 CD44_E26_F 0.85 0.042593 0.014825 864 HLA-DPB1_E2_R −0.16 0.042985 0.014931 865 ABO_E110_F 0.21 0.043 0.014931 866 TSG101_P257_R −0.13 0.043755 0.015176 867 NQO1_P345_R 0.27 0.043821 0.015181 868 IGFBP7_P371_F 0.69 0.04404 0.01524 869 IGFBP2_P353_R 0.28 0.044259 0.015298 870 PADI4_P1158_R −0.25 0.044789 0.015463 871 BMPR1A_E88_F −0.16 0.046339 0.015971 872 TYRO3_P501_F 0.15 0.046366 0.015971 873 HPN_P374_R 0.23 0.046459 0.015985 874 LRP2_E20_F 0.40 0.04715 0.016204 875 GP1BB_P278_R 0.28 0.047311 0.016241 876 ACTG2_P346_F −0.16 0.047758 0.016376 877 CD44_P87_F 0.47 0.047887 0.016401 878 IL10_P348_F −0.27 0.049343 0.016881 879 SLIT2_E111_R 0.16 0.049937 0.017065 880 MLH3_E72_F 0.13 0.050128 0.01711 881 MOS_P746_F −0.26 0.051713 0.017613 882 VIM_P343_R 0.46 0.051719 0.017613 883 CD34_P339_R 0.21 0.052572 0.017884 884 CSTB_E410_F −0.14 0.052839 0.017937 885 TUSC3_P85_R 0.16 0.052849 0.017937 886 FGFR3_E297_R 0.12 0.053802 0.01824 887 SRC_P297_F −0.25 0.053887 0.018248 888 IL6_E168_F 0.28 0.054222 0.018341 889 RIPK4_P172_F −0.11 0.056409 0.01906 890 CTNNA1_P382_R 0.13 0.056718 0.019136 891 ABCA1_E120_R 0.22 0.056822 0.019136 892 ACVR1_E328_R 0.27 0.056826 0.019136 893 ONECUT2_E96_F 0.26 0.057195 0.019239 894 PTPNS1_E433_R 0.38 0.057328 0.019262 895 ERG_E28_F −0.31 0.057511 0.019302 896 IGF1R_P325_R 0.08 0.058264 0.019533 897 WNT1_E157_F 0.34 0.058579 0.019616 898 SGCE_P250_R −0.21 0.05903 0.019745 899 CTNNA1_P185_R 0.17 0.059125 0.019755 900 KRT1_P798_R −0.19 0.060224 0.0201 901 GSTP1_E322_R 0.27 0.060339 0.020116 902 KCNQ1_P546_R 0.21 0.060618 0.020187 903 UGT1A1_P564_R −0.16 0.060695 0.02019 904 CPA4_P961_R −0.13 0.061916 0.020573 905 HIC-1_seq_48_S103_R −0.33 0.062661 0.020777 906 SGCE_E149_F 0.16 0.062667 0.020777 907 VAV2_E58_F −0.18 0.063375 0.020989 908 BCAM_P205_F 0.15 0.063716 0.021078 909 SHH_P104_R 0.30 0.063784 0.021078 910 SYK_E372_F 0.07 0.064822 0.021397 911 ERN1_P809_R 0.23 0.065469 0.021587 912 TMEFF1_E180_R 0.19 0.065863 0.021693 913 RASA1_E107_F 0.09 0.06609 0.02174 914 ITGB4_E144_F −0.12 0.066221 0.02174 915 ERBB4_P255_F 0.39 0.066246 0.02174 916 LOX_P71_F 0.44 0.066293 0.02174 917 P2RX7_E323_R 0.26 0.066466 0.021773 918 MATK_P190_R −0.18 0.06684 0.021858 919 IGFBP6_E47_F −0.12 0.066873 0.021858 920 RBP1_P426_R 0.25 0.067661 0.022092 921 FABP3_P598_F 0.20 0.06858 0.022368 922 TJP1_P390_F 0.48 0.070619 0.023008 923 CLK1_P538_F −0.16 0.070996 0.023105 924 TIMP2_P267_F 0.22 0.071478 0.023237 925 TEK_E75_F 0.21 0.071771 0.023307 926 ABL2_P459_R −0.16 0.072325 0.023462 927 IL11_P11_R 0.14 0.072837 0.023593 928 DAPK1_P10_F 0.13 0.072887 0.023593 929 EFNA1_P591_R 0.12 0.073568 0.023788 930 AHR_E103_F 0.09 0.073991 0.023899 931 SEPT9_P374_F 0.27 0.074589 0.024066 932 PTCH_E42_F 0.17 0.075611 0.02437 933 EDN1_P39_R 0.10 0.076622 0.024645 934 FAT_P973_R 0.22 0.076627 0.024645 935 TFPI2_P152_R 0.29 0.077732 0.024973 936 PALM2-AKAP2_P183_R 0.15 0.078432 0.025171 937 TGFB3_E58_R −0.28 0.078814 0.025255 938 SMARCA3_E20_F 0.46 0.078939 0.025255 939 ODC1_P424_F 0.14 0.078945 0.025255 940 ABCA1_P45_F 0.47 0.079213 0.025314 941 TUBB3_E91_F −0.28 0.0794 0.025347 942 PTEN_P438_F 0.08 0.080186 0.025552 943 RAB32_P493_R 0.26 0.080213 0.025552 944 MST1R_P392_F 0.45 0.080998 0.025775 945 RIPK4_E166_F −0.15 0.08146 0.025895 946 EPHB4_P313_R −0.13 0.081968 0.026028 947 EXT1_E197_F −0.10 0.082187 0.02607 948 GNMT_E126_F 0.31 0.082695 0.026204 949 PPARG_E178_R 0.23 0.083055 0.02629 950 CSF1_P339_F 0.24 0.083599 0.026435 951 SEMA3F_E333_R 0.16 0.084934 0.026829 952 EPHB3_P569_R 0.20 0.085173 0.026852 953 KRT13_P341_R −0.27 0.085186 0.026852 954 IHH_P529_F 0.25 0.085396 0.02689 955 ABCC5_P444_F 0.11 0.085858 0.027007 956 EPHA3_E156_R 0.30 0.086535 0.027192 957 NDN_E131_R −0.15 0.087025 0.027317 958 CD9_E14_R 0.10 0.087289 0.027371 959 HDAC5_E298_F −0.09 0.08769 0.027468 960 S100A4_E315_F 0.26 0.088241 0.027612 961 IL1B_P829_F −0.12 0.089268 0.027905 962 XRCC1_P681_R −0.23 0.089429 0.027926 963 ITGA2_E120_F 0.12 0.089645 0.027964 964 ITPR3_E86_R 0.15 0.089821 0.02799 965 CAPG_E228_F −0.23 0.09029 0.028107 966 IGFBP1_P12_R −0.22 0.091504 0.028455 967 TFPI2_E141_F 0.24 0.093309 0.028987 968 ALK_E183_R 0.15 0.094123 0.029189 969 VIM_P811_R 0.31 0.094153 0.029189 970 RARRES1_P426_R −0.23 0.094519 0.029272 971 FHIT_E19_R 0.08 0.095136 0.029433 972 GSTP1_P74_F 0.08 0.095569 0.029537 973 MYCN_P464_R 0.28 0.097073 0.02997 974 RIPK1_P744_R 0.25 0.097683 0.030128 975 PLAGL1_P236_R −0.15 0.098099 0.030225 976 COPG2_P298_F 0.19 0.101133 0.031128 977 DLL1_P832_F 0.25 0.101686 0.031266 978 XPC_P226_R −0.10 0.103449 0.031776 979 TCF4_P175_R 0.33 0.103637 0.031779 980 IGSF4_P454_F 0.23 0.103671 0.031779 981 PTK2B_P673_R 0.08 0.10409 0.031875 982 RARB_P60_F 0.17 0.104839 0.032072 983 MAPK14_P327_R −0.17 0.105591 0.032269 984 LIMK1_P709_R −0.25 0.106276 0.032445 985 PPAT_E170_R 0.15 0.106942 0.032615 986 SKI_E465_R −0.11 0.107431 0.032731 987 CHFR_P501_F 0.25 0.10805 0.032887 988 FANCE_P356_R 0.23 0.108593 0.033018 989 COL1A1_P5_F 0.23 0.109189 0.033147 990 CDKN1A_E101_F −0.09 0.109337 0.033147 991 MDS1_E45_F −0.09 0.109347 0.033147 992 YES1_P600_F 0.07 0.111985 0.033913 993 ESR2_E66_F 0.36 0.112398 0.034004 994 ENC1_P484_R 0.34 0.112592 0.034028 995 NKX3-1_P146_F 0.22 0.113082 0.034142 996 CSF1_P217_F 0.20 0.113384 0.034199 997 PGF_E33_F 0.17 0.114019 0.034322 998 ROR2_E112_F 0.20 0.114022 0.034322 999 ALPL_P278_F 0.55 0.11513 0.034621 1000 PTGS1_E80_F 0.21 0.116052 0.034864 1001 FN1_E469_F 0.33 0.119483 0.035858 1002 BMP2_P1201_F 0.12 0.11981 0.035921 1003 MMP7_P613_F −0.11 0.119935 0.035922 1004 SMAD4_P474_R 0.10 0.122181 0.036559 1005 SEMA3B_E96_F 0.15 0.123084 0.036792 1006 CAV1_P169_F 0.16 0.12378 0.036964 1007 HPN_P823_F −0.24 0.1241 0.037023 1008 PTHLH_P757_F −0.15 0.126525 0.037708 1009 FASTK_P598_R −0.15 0.126934 0.037793 1010 NOTCH2_P312_R −0.06 0.127748 0.037998 1011 CTSL_P264_R 0.18 0.128332 0.038134 1012 TMEFF1_P234_F 0.18 0.128788 0.038231 1013 GRB10_P260_F 0.33 0.129244 0.038329 1014 TGFB2_P632_F 0.43 0.129863 0.038474 1015 CDKN2A_E121_R −0.08 0.13051 0.038628 1016 TRIP6_P1274_R −0.18 0.13467 0.03982 1017 IGFBP7_P297_F 0.12 0.135037 0.039889 1018 MMP14_P13_F 0.22 0.13621 0.040196 1019 CDK10_E74_F −0.07 0.137131 0.040429 1020 GSTM2_P453_R 0.17 0.137926 0.040623 1021 MLLT6_P957_F −0.12 0.138546 0.040766 1022 HSD17B12_P97_F 0.32 0.142271 0.041821 1023 IFNGR1_P307_F 0.10 0.143345 0.042095 1024 MSH2_P1008_F −0.15 0.144064 0.042265 1025 PLXDC2_P914_R 0.21 0.146471 0.04293 1026 GPR116_P850_F 0.14 0.146906 0.043015 1027 GATA6_P21_R −0.12 0.148147 0.043336 1028 CTGF_P693_R 0.21 0.150328 0.043932 1029 CTGF_E156_F 0.32 0.151585 0.044256 1030 HLA-DQA2_P282_R −0.13 0.152543 0.044492 1031 MEG3_P235_F −0.16 0.15506 0.045183 1032 CDH3_P87_R 0.31 0.158055 0.046004 1033 SEMA3A_P343_F 0.21 0.158184 0.046004 1034 RHOC_P536_F 0.12 0.160801 0.04672 1035 MYBL2_P211_F 0.37 0.162641 0.047209 1036 TFRC_P414_R 0.24 0.163839 0.047489 1037 JAK2_P772_R 0.10 0.163922 0.047489 1038 COL4A3_P545_F 0.15 0.164976 0.047748 1039 PCDH1_P264_F −0.22 0.16556 0.047871 1040 PTGS2_P308_F −0.16 0.166178 0.048004 1041 TNK1_P221_F −0.14 0.16788 0.048449 1042 NEU1_P745_F 0.30 0.168238 0.048506 1043 NRAS_P12_R 0.35 0.169916 0.048943 1044 BMP4_P123_R 0.18 0.171445 0.049336 1045 BCL3_P1038_R 0.05 0.171826 0.049398 1046 LAMC1_P808_F −0.05 0.173697 0.049888 1047 *Positive coefficient indicates increased methylation in tumors relative to normal

SUPPLEMENTAL TABLE 19 CpG methylation locus-by-locus analysis of infant blood samples from healthy newborn infants compared to newborn infant bloods from individuals who went on to develop childhood leukemia Regres- sion co- GENE_CpG efficient* P-value Q-value Rank MCAM_P265_R −0.34 0.0E+00 3.9E−04 1 MCM2_P241_R −0.34 2.0E−06 7.6E−04 2 MYB_P673_R −0.25 5.6E−05 0.02 3 HOXA11_P92_R −0.30 4.5E−04 0.10 4 COPG2_P298_F −0.57 0.001 0.10 5 APBA1_E99_R −0.47 0.001 0.10 6 BMP4_P123_R −0.21 0.001 0.10 7 RARA_P176_R −0.30 0.001 0.10 8 MST1R_P392_F −0.34 0.001 0.10 9 MST1R_P87_R −0.19 0.001 0.10 10 GNMT_P197_F −0.14 0.001 0.10 11 FGF9_P1404_F −0.15 0.001 0.10 12 FGF9_P862_R −0.11 0.001 0.10 13 HIC2_P528_R −0.21 0.002 0.10 14 ROR1_P6_F −0.28 0.002 0.11 15 DUSP4_P925_R −0.25 0.002 0.11 16 LAT_E46_F −0.27 0.002 0.12 17 CASP3_P420_R −0.30 0.002 0.12 18 MYCN_E77_R −0.18 0.002 0.12 19 p16_seq_47_S85_F −0.21 0.003 0.12 20 SIN3B_P607_F −0.23 0.003 0.12 21 ITGA6_P298_R −0.20 0.003 0.13 22 MAP3K1_E81_F −0.39 0.003 0.13 23 IGFBP5_E144_F −0.26 0.004 0.14 24 LTB4R_E64_R −0.23 0.004 0.14 25 TFPI2_E141_F −0.34 0.004 0.14 26 INHA_P1189_F −0.18 0.004 0.15 27 TGFA_P558_F −0.26 0.004 0.15 28 PPARD_P846_F −0.34 0.005 0.15 29 TES_P182_F −0.29 0.005 0.15 30 PTPRG_E40_R −0.33 0.005 0.15 31 MAF_P826_R −0.57 0.005 0.15 32 FAS_P65_F −0.25 0.006 0.15 33 RRAS_P100_R −0.49 0.006 0.15 34 EPHA3_E156_R −0.29 0.006 0.15 35 EPHA5_E158_R −0.17 0.006 0.15 36 MPL_P657_F −0.24 0.006 0.15 37 EYA4_P794_F −0.24 0.006 0.15 38 DST_E31_F −0.21 0.006 0.15 39 TMEFF2_P210_R −0.42 0.006 0.15 40 MLH3_E72_F −0.36 0.007 0.16 41 SMARCA4_P362_R −0.32 0.008 0.18 42 DIO3_P90_F −0.20 0.008 0.18 43 OPCML_P71_F −0.19 0.008 0.18 44 FN1_P229_R −0.27 0.009 0.18 45 PDE1B_E141_F −0.15 0.009 0.18 46 ADAMTS12_E52_R −0.20 0.010 0.19 47 ZMYND10_E77_R −0.39 0.010 0.20 48 TNFSF10_E53_F −0.28 0.010 0.20 49 IGF1_E394_F −0.18 0.011 0.20 50 EPHA8_P256_F −0.19 0.011 0.20 51 EPHB1_E202_R −0.13 0.011 0.20 52 EVI2A_E420_F −0.21 0.011 0.20 53 WNT2B_P1195_F −0.21 0.011 0.20 54 EPHB6_P827_R −0.09 0.012 0.20 55 EIF2AK2_E103_R −0.20 0.013 0.22 56 DHCR24_P652_R −0.09 0.013 0.22 57 BMP6_P163_F −0.25 0.013 0.22 58 EVI2A_P94_R −0.31 0.014 0.22 59 RAD54B_P227_F −0.16 0.014 0.22 60 RIPK4_P172_F −0.14 0.014 0.22 61 DCC_P471_R −0.24 0.015 0.23 62 SNURF_P2_R 0.15 0.015 0.23 63 SEMA3C_E49_R −0.24 0.015 0.23 64 ELK3_P514_F −0.39 0.016 0.23 65 MAF_E77_R −0.33 0.017 0.24 66 FGFR2_P460_R −0.16 0.017 0.24 67 FLT4_E206_F −0.11 0.017 0.24 68 FLT4_P180_R −0.17 0.018 0.24 69 CCL3_E53_R −0.17 0.019 0.26 70 RUNX1T1_E145_R −0.17 0.020 0.26 71 TDGF1_E53_R −0.13 0.020 0.26 72 TSC2_E140_F −0.16 0.020 0.26 73 HIF1A_P488_F −0.32 0.021 0.26 74 CD34_E20_R −0.14 0.021 0.26 75 AREG_P217_R −0.15 0.021 0.26 76 FVT1_P225_F −0.13 0.022 0.26 77 IFNGR2_E164_F 0.19 0.022 0.26 78 RARRES1_P426_R −0.27 0.022 0.26 79 PGF_P320_F −0.19 0.022 0.26 80 BLK_P668_R −0.19 0.022 0.26 81 PTHLH_P757_F −0.18 0.022 0.26 82 NNAT_P544_R −0.14 0.023 0.27 83 CSPG2_P82_R −0.23 0.023 0.27 84 APOC2_P377_F −0.18 0.024 0.27 85 TNFRSF1B_E5_F −0.20 0.024 0.27 86 FOSL2_E384_R −0.21 0.025 0.27 87 NTRK2_P395_R −0.30 0.025 0.27 88 F2R_P839_F −0.15 0.025 0.27 89 DUSP4_E61_F −0.16 0.026 0.27 90 FZD9_E458_F −0.17 0.026 0.27 91 ABL2_P459_R −0.20 0.026 0.27 92 ID1_P880_F −0.17 0.026 0.27 93 MAPK12_E165_R −0.14 0.027 0.27 94 TJP1_P326_R −0.24 0.028 0.27 95 CDH1_P52_R −0.24 0.028 0.27 96 FABP3_E113_F −0.18 0.028 0.27 97 PALM2-AKAP2_P420_R −0.19 0.028 0.27 98 MMP10_E136_R −0.15 0.029 0.27 99 TNFRSF1B_P167_F −0.25 0.029 0.27 100 WEE1_P924_R −0.14 0.029 0.27 101 PTK6_E50_F −0.15 0.030 0.27 102 IPF1_P234_F −0.22 0.030 0.27 103 TIMP2_P267_F −0.17 0.030 0.27 104 EDN1_P39_R −0.16 0.031 0.28 105 ONECUT2_E96_F −0.20 0.031 0.28 106 EPHA7_E6_F −0.18 0.031 0.28 107 CCND1_E280_R −0.17 0.032 0.28 108 ADCYAP1_E163_R −0.48 0.033 0.28 109 XPC_P226_R −0.10 0.033 0.28 110 ISL1_P379_F −0.17 0.033 0.29 111 PDGFB_P719_F −0.14 0.034 0.29 112 EPHA7_P205_R −0.15 0.035 0.29 113 BMP3_P56_R −0.28 0.035 0.29 114 KCNK4_E3_F −0.12 0.036 0.30 115 PENK_E26_F −0.08 0.037 0.30 116 RYK_P493_F −0.31 0.038 0.30 117 COL6A1_P283_F −0.21 0.038 0.30 118 GSTM2_P453_R −0.15 0.039 0.30 119 GPX1_E46_R −0.25 0.039 0.30 120 CCNA1_P216_F −0.34 0.040 0.30 121 SEMA3B_E96_F −0.13 0.040 0.30 122 MYLK_P469_R −0.13 0.040 0.30 123 HPSE_P93_F −0.16 0.041 0.30 124 CAV1_P169_F −0.16 0.041 0.30 125 ESR1_P151_R −0.31 0.042 0.30 126 TMEFF2_P152_R −0.15 0.042 0.30 127 WNT1_P79_R −0.13 0.042 0.30 128 NPY_E31_R −0.15 0.042 0.30 129 GSTM2_P109_R −0.24 0.042 0.30 130 HOXB13_E21_F −0.14 0.043 0.30 131 ERBB3_E331_F −0.22 0.043 0.30 132 CFTR_P115_F −0.25 0.043 0.30 133 IL12B_P392_R −0.26 0.043 0.30 134 S100A4_P887_R −0.14 0.043 0.30 135 IL6_E168_F −0.16 0.044 0.30 136 MUC1_P191_F −0.22 0.044 0.30 137 CASP8_E474_F −0.11 0.044 0.30 138 COL4A3_E205_R −0.13 0.045 0.30 139 VAMP8_P114_F −0.21 0.045 0.30 140 ACVR1C_P115_R −0.11 0.045 0.30 141 IGFBP7_P297_F −0.12 0.045 0.30 142 PAX6_P1121_F −0.15 0.045 0.30 143 HIC1_E151_F −0.24 0.046 0.30 144 MAPK4_E273_R −0.12 0.046 0.30 145 HDAC9_P137_R −0.19 0.046 0.30 146 PHLDA2_P622_F −0.17 0.047 0.30 147 CDK6_E256_F −0.15 0.047 0.30 148 MYOD1_E156_F −0.20 0.047 0.30 149 HIC-1_seq_48_S103 −0.29 0.047 0.30 150 CRIP1_P274_F −0.13 0.048 0.30 151 TFDP1_P543_R −0.13 0.048 0.30 152 JUNB_P1149_R −0.11 0.048 0.30 153 TFAP2C_P765_F 0.25 0.049 0.30 154 EFNB3_E17_R −0.12 0.049 0.30 155 PLXDC1_E71_F −0.15 0.049 0.30 156 WNT2_P217_F −0.16 0.049 0.30 157 IGFBP3_P1035_F −0.21 0.050 0.30 158 TMEM63A_E63_F −0.27 0.050 0.30 159 OPCML_E219_R −0.19 0.051 0.30 160 HLA-DRA_P132_R −0.21 0.051 0.30 161 IGFBP3_E65_R −0.10 0.051 0.30 162 FER_E119_F −0.18 0.051 0.30 163 SLC14A1_P369_R −0.10 0.051 0.30 164 PLAGL1_E68_R 0.18 0.052 0.30 165 VIM_P811_R −0.26 0.053 0.30 166 USP29_E274_F −0.12 0.053 0.30 167 TJP2_P330_R −0.17 0.053 0.30 168 MET_E333_F −0.25 0.054 0.30 169 TIMP2_E394_R −0.19 0.054 0.30 170 ADCYAP1_P398_F −0.20 0.054 0.30 171 NEU1_P745_F −0.25 0.055 0.31 172 TPEF_seq_44_S88_R −0.17 0.055 0.31 173 FHIT_E19_R −0.18 0.056 0.31 174 MEST_E150_F −0.21 0.056 0.31 175 AOC3_P890_R −0.14 0.057 0.31 176 GATA6_P21_R −0.12 0.058 0.32 177 FRZB_P406_F −0.24 0.059 0.32 178 ETV1_P515_F −0.16 0.059 0.32 179 KCNQ1_P546_R −0.24 0.059 0.32 180 CCND3_P435_F −0.12 0.060 0.32 181 PLXDC1_P236_F −0.15 0.060 0.32 182 KLK10_P268_R −0.19 0.061 0.32 183 HLA-DRA_P77_R −0.25 0.062 0.32 184 TGFBR3_P429_F −0.29 0.062 0.32 185 CTNNB1_P757_F −0.20 0.062 0.32 186 PLAGL1_P236_R 0.13 0.062 0.32 187 TP73_E155_F −0.14 0.062 0.32 188 RAB32_E314_R −0.19 0.063 0.32 189 CDKN2B_seq_50_S294_(—) 0.34 0.064 0.32 190 SOX1_P1018_R −0.21 0.065 0.32 191 FGFR3_P1152_R −0.16 0.065 0.32 192 CHD2_P667_F −0.14 0.065 0.32 193 NDN_E131_R −0.08 0.066 0.32 194 CASP6_P230_R −0.18 0.067 0.32 195 GP1BB_E23_F −0.14 0.067 0.32 196 PADI4_P1011_R −0.09 0.067 0.32 197 SNURF_E256_R −0.10 0.067 0.32 198 COMT_E401_F −0.12 0.069 0.33 199 IGSF4_P86_R −0.28 0.069 0.33 200 PSCA_P135_F −0.09 0.069 0.33 201 GPX1_P194_F −0.19 0.069 0.33 202 CD44_E26_F −0.14 0.070 0.33 203 PLAUR_P82_F −0.39 0.070 0.33 204 SOX2_P546_F −0.19 0.072 0.34 205 NTRK3_P636_R −0.33 0.072 0.34 206 MT1A_E13_R −0.18 0.073 0.34 207 RIPKl_P868_F −0.14 0.073 0.34 208 SMARCA3_P17_R −0.23 0.073 0.34 209 ERBB3_P870_R −0.22 0.074 0.34 210 IL13_E75_R −0.17 0.075 0.34 211 USP29_P282_R −0.15 0.075 0.34 212 SEPT5_P464_R 0.11 0.075 0.34 213 ABCB4_E429_F −0.16 0.078 0.34 214 SFN_E118_F −0.12 0.078 0.34 215 CCR5_P630_R −0.11 0.078 0.34 216 PIK3R1_P307_F −0.12 0.078 0.34 217 EPO_P162_R −0.11 0.079 0.35 218 MAPK9_P1175_F −0.14 0.080 0.35 219 IGFBP1_E48_R −0.16 0.080 0.35 220 EDNRB_P148_R −0.16 0.080 0.35 221 NKX3-1_P871_R −0.16 0.080 0.35 222 DDR2_P743_R −0.14 0.081 0.35 223 PTCH_E42_F −0.09 0.081 0.35 224 ASCL1_E24_F −0.21 0.082 0.35 225 INS_P804_R −0.19 0.082 0.35 226 RAD50_P191_F −0.12 0.082 0.35 227 ITGB4_P517_F −0.12 0.082 0.35 228 PRKCDBP_E206_F −0.18 0.083 0.35 229 IL1RN_E42_F −0.20 0.084 0.35 230 ATP10A_P147_F −0.19 0.084 0.35 231 ZNF264_E48_R −0.29 0.085 0.35 232 TWIST1_P44_R −0.23 0.085 0.35 233 TNFRSF10B_P108_R −0.18 0.085 0.35 234 CDKN1C_P626_F −0.15 0.086 0.35 235 CCKAR_P270_F −0.14 0.086 0.35 236 RASGRF1_E16_F −0.14 0.086 0.35 237 PWCR1_E81_R −0.15 0.087 0.35 238 ER_seq_a1_S60_F −0.17 0.087 0.35 239 CASP10_E139_F −0.16 0.088 0.35 240 TSG101_P139_R −0.19 0.088 0.35 241 FOLR1_E368_R −0.20 0.089 0.35 242 TNFRSF10B_E198_R −0.14 0.089 0.35 243 IRF5_E101_F −0.24 0.091 0.35 244 CDH17_E31_F −0.14 0.091 0.35 245 APOA1_P261_F −0.12 0.091 0.35 246 GABRB3_E42_F −0.15 0.091 0.35 247 BSG_P211_R −0.28 0.092 0.35 248 IRAK3_P13_F −0.16 0.092 0.35 249 RUNX3_E27_R −0.15 0.093 0.36 250 EPHX1_P1358_R −0.08 0.093 0.36 251 HLF_E192_F −0.16 0.094 0.36 252 IGFBP3_P423_R −0.18 0.095 0.36 253 BCL6_P248_R −0.24 0.095 0.36 254 ACVR2B_E27_R −0.17 0.095 0.36 255 TNK1_P221_F −0.13 0.096 0.36 256 SHB_P691_R −0.17 0.097 0.36 257 TRIP6_P1090_F −0.21 0.098 0.36 258 KRT13_P676_F −0.12 0.098 0.36 259 MLH3_P25_F −0.09 0.098 0.36 260 PTCH2_P37_F −0.14 0.099 0.36 261 TSP50_P137_F −0.29 0.099 0.36 262 EFNA1_P7_F −0.17 0.099 0.36 263 SFRP1_E398_R −0.27 0.099 0.36 264 MUC1_E18_R 0.14 0.099 0.36 265 DBC1_E204_F −0.18 0.100 0.36 266 NTRK2_P10_F −0.19 0.100 0.36 267 ACVR1_E328_R −0.12 0.100 0.36 268 TWIST1_E117_R 0.32 0.100 0.36 269 ABCC2_P88_F −0.17 0.101 0.36 270 DAB2IP_E18_R −0.12 0.102 0.36 271 GSTP1_E322_R 0.25 0.102 0.36 272 ITK_E166_R −0.15 0.102 0.36 273 NGFR_P355_F −0.13 0.103 0.36 274 GABRB3_P92_F −0.08 0.103 0.36 275 CEBPA_P706_F −0.18 0.103 0.36 276 DBC1_P351_R −0.20 0.104 0.36 277 LIG4_P194_F −0.22 0.105 0.36 278 CTNNA1_P382_R −0.14 0.106 0.36 279 POMC_E254_F −0.13 0.106 0.36 280 SMARCA3_P109_R −0.21 0.107 0.36 281 HLA-DPB1_E2_R −0.14 0.107 0.36 282 H19_P1411_R −0.09 0.109 0.36 283 TMEFF1_P626_R −0.11 0.109 0.36 284 CHI3L2_P226_F −0.08 0.110 0.36 285 MXI1_P75_R −0.22 0.110 0.36 286 GABRA5_P862_R −0.12 0.110 0.36 287 MGMT_P281_F −0.14 0.110 0.36 288 ITK_P114_F −0.15 0.110 0.36 289 MYOD1_P50_F −0.15 0.111 0.36 290 RBP1_E158_F −0.13 0.112 0.36 291 PAX6_E129_F −0.14 0.112 0.36 292 BMP3_E147_F −0.12 0.112 0.36 293 ETS1_E253_R −0.12 0.112 0.36 294 TSP50_E21_R −0.14 0.113 0.36 295 MCC_E23_R −0.12 0.113 0.36 296 AFF3_P122_F −0.20 0.113 0.36 297 TGFB1_P833_R −0.13 0.114 0.36 298 IL11_P11_R −0.16 0.114 0.36 299 INSR_E97_F −0.14 0.114 0.36 300 CRK_P721_F −0.17 0.114 0.36 301 MAP2K6_E297_F −0.30 0.116 0.37 302 SPARC_P195_F −0.20 0.116 0.37 303 HHIP_P578_R −0.22 0.117 0.37 304 MYLK_E132_R −0.07 0.117 0.37 305 PTPRH_E173_F −0.09 0.118 0.37 306 FGF5_P238_R −0.20 0.118 0.37 307 IGFBP6_E47_F −0.09 0.119 0.37 308 KRT1_P798_R −0.10 0.119 0.37 309 EGF_P242_R −0.08 0.119 0.37 310 RHOH_P953_R −0.13 0.119 0.37 311 GNG7_E310_R −0.18 0.119 0.37 312 CD81_P211_F −0.16 0.120 0.37 313 DSC2_P407_R −0.17 0.121 0.37 314 APP_E8_F −0.17 0.122 0.37 315 DIO3-E230_R −0.09 0.122 0.37 316 CTLA4_E176_R −0.11 0.124 0.37 317 LRRC32_E157_F −0.18 0.125 0.37 318 BMPR1A_E88_F 0.14 0.125 0.37 319 JAG2_P264_F −0.16 0.125 0.37 320 DNAJC15_P65_F −0.14 0.126 0.37 321 FGFR1_P204_F −0.19 0.126 0.37 322 PKD2-P336_R −0.09 0.127 0.37 323 GDF10_E39_F −0.08 0.127 0.37 324 PRSS1_P1249_R −0.14 0.128 0.37 325 GLI2_P295_F −0.09 0.128 0.37 326 HLA-F_E402_F −0.23 0.129 0.37 327 EPO_E244_R −0.34 0.129 0.37 328 DDIT3_P1313_R −0.11 0.129 0.37 329 IL8_E118_R 0.18 0.130 0.37 330 ABCG2_P178_R −0.09 0.130 0.37 331 NID1_P714_R −0.12 0.130 0.37 332 IFNG_E293_F −0.12 0.131 0.38 333 GNG7_P903_F −0.11 0.132 0.38 334 MEG3_P235_F −0.07 0.132 0.38 335 MMP1_P397_R −0.17 0.132 0.38 336 CD40_P372_R −0.17 0.133 0.38 337 CSK_P740_R 0.20 0.133 0.38 338 DIRAS3_P745_F −0.10 0.134 0.38 339 PXN_P308_F −0.13 0.134 0.38 340 FLT1_P302_F −0.22 0.135 0.38 341 PITX2_P183_R 0.16 0.136 0.38 342 ERG_E28_F −0.13 0.136 0.38 343 NOTCH4_P938_F −0.09 0.137 0.38 344 PKD2_P287_R −0.16 0.137 0.38 345 PHLDA2_E159_R −0.10 0.138 0.38 346 HRASLS_P353_R 0.14 0.138 0.38 347 FABP3_P598_F −0.10 0.139 0.38 348 KIAA1804_P689_R 0.17 0.140 0.38 349 SFTPA1_E340_R −0.18 0.141 0.38 350 CHD2_P451_F −0.12 0.141 0.38 351 CD40_E58_R −0.16 0.141 0.38 352 SLC14A1_E295_F −0.08 0.142 0.38 353 EPS8_E231_F 0.13 0.142 0.38 354 ZIM3_E203_F −0.17 0.143 0.38 355 APOA1_P75_F 0.44 0.143 0.38 356 XRCC1_P681_R −0.13 0.144 0.38 357 ROR2_E112_F −0.13 0.144 0.38 358 KLF5_P13_F 0.13 0.144 0.38 359 YES1_P216_F −0.19 0.146 0.39 360 PTPN6_E171_R 0.24 0.147 0.39 361 OAT_P465_F −0.11 0.147 0.39 362 MAS1_P469_R −0.09 0.148 0.39 363 ALK_E183_R −0.07 0.148 0.39 364 IGF2AS_P203_F 0.18 0.149 0.39 365 PLAT_E158_F −0.18 0.150 0.39 366 EFNB3_P442_R −0.13 0.150 0.39 367 KIAA0125_E29_F −0.10 0.151 0.39 368 DDR1_P332_R −0.22 0.151 0.39 369 CSF2_E248_R −0.10 0.152 0.39 370 FLJ20712_P984_R −0.15 0.152 0.39 371 EMR3_P39_R −0.19 0.153 0.39 372 MAPK14_P327_R −0.18 0.154 0.39 373 ACTG2_P455_R −0.13 0.155 0.39 374 SMARCA3_E20_F 0.19 0.155 0.39 375 CDKN1B_P1161_F −0.11 0.155 0.39 376 KRT5_P308_F −0.09 0.157 0.40 377 ABCA1_P45_F −0.21 0.157 0.40 378 LMO1_E265_R −0.16 0.157 0.40 379 INSR_P1063_R −0.25 0.158 0.40 380 CDH11_P354_R −0.11 0.158 0.40 381 CYP1B1_E83_R −0.19 0.159 0.40 382 PCGF4_P760_R −0.12 0.159 0.40 383 F2R_P88_F −0.20 0.159 0.40 384 TRPM5_E87_F −0.11 0.161 0.40 385 TAL1_P817_F −0.14 0.161 0.40 386 FANCE_P356_R −0.11 0.161 0.40 387 DCC_P177_F −0.19 0.162 0.40 388 DES_E228_R −0.11 0.163 0.40 389 NOTCH3_E403_F −0.19 0.164 0.40 390 NCL_P1102_F −0.10 0.164 0.40 391 PEG10_P978_R −0.11 0.165 0.40 392 MPO_P883_R −0.11 0.165 0.40 393 IGFBP6_P328_R −0.13 0.165 0.40 394 ERCC1_P354_F 0.21 0.166 0.40 395 IL18BP_E285_F −0.08 0.169 0.41 396 CTLA4_P1128_F −0.07 0.170 0.41 397 PTCH2_P568_R −0.10 0.170 0.41 398 TMPRSS4_E83_F −0.10 0.170 0.41 399 FGF8_P473_F −0.11 0.170 0.41 400 SLC22A18_P472_R −0.08 0.173 0.41 401 FLT3_P302_F −0.14 0.174 0.41 402 CD81_P272_R −0.11 0.174 0.41 403 HOXA11_E35_F −0.13 0.175 0.41 404 CCND1_P343_R 0.21 0.175 0.41 405 E2F5_P516_R −0.13 0.175 0.41 406 RAP1A_P285_R −0.08 0.176 0.41 407 EMR3_P1297_R −0.12 0.176 0.41 408 STK11_P295_R −0.18 0.177 0.41 409 TNFRSF10C_P7_F −0.10 0.177 0.41 410 PENK_P447_R −0.18 0.178 0.41 411 IL16_P93_R −0.08 0.178 0.41 412 BLK_P14_F −0.16 0.178 0.41 413 RUNX3_P393_R −0.13 0.180 0.41 414 FGFR3_E297_R −0.11 0.180 0.41 415 IGFBP1_P12_R −0.15 0.180 0.41 416 B3GALT5_P330_F −0.08 0.181 0.41 417 CSPG2_E38_F −0.11 0.181 0.41 418 ZNFN1A1_E102_F −0.09 0.181 0.41 419 COL4A3_P545_F −0.11 0.182 0.41 420 AKT1_P310_R −0.10 0.182 0.41 421 COL18A1_P494_R −0.10 0.183 0.41 422 RET_seq_54_S260_F −0.12 0.184 0.41 423 AIM2_E208_F −0.13 0.185 0.41 424 FGF1_E5_F −0.08 0.186 0.41 425 FGF7_P44_F −0.10 0.186 0.41 426 FZD7_E296_F 0.13 0.187 0.41 427 SEMA3F_E333_R −0.12 0.187 0.41 428 SIN3B_P514_R −0.14 0.188 0.41 429 HBII-52_E142_F 0.20 0.188 0.41 430 CAPG_E228_F −0.21 0.188 0.41 431 PALM2-AKAP2_P183 −0.11 0.188 0.41 432 CDH13_E102_F −0.19 0.189 0.41 433 CTSD_P726_F −0.10 0.189 0.41 434 S100A2_E36_R −0.10 0.189 0.41 435 SEMA3B_P110_R −0.11 0.190 0.41 436 SRC_E100_R −0.08 0.190 0.41 437 FRK_P36_F −0.11 0.190 0.41 438 KDR_P445_R −0.16 0.191 0.42 439 RIPK2_E123_F −0.10 0.194 0.42 440 DDR1_E23_R −0.12 0.194 0.42 441 EVI1_P30_R −0.15 0.195 0.42 442 GRB10_E85_R −0.12 0.195 0.42 443 HBEGF_P32_R −0.20 0.195 0.42 444 NES_P239_R 0.15 0.195 0.42 445 HOXA9_P303_F −0.16 0.196 0.42 446 CDKN1C_P6_R −0.10 0.196 0.42 447 CTTN_E29_R 0.26 0.197 0.42 448 AGXT_P180_F 0.12 0.197 0.42 449 JAK3_P156_R −0.15 0.198 0.42 450 TYRO3_P501_F −0.16 0.198 0.42 451 ZNFN1A1_P179_F −0.14 0.198 0.42 452 MT1A_P49_R −0.16 0.201 0.42 453 GAS1_E22_F −0.13 0.202 0.42 454 HIC2_P498_F −0.10 0.203 0.42 455 GLI2_E90_F −0.15 0.203 0.42 456 P2RX7_P597_F −0.11 0.204 0.42 457 PGR_P790_F −0.09 0.204 0.42 458 CD1A_P414_R −0.17 0.204 0.43 459 ODC1_P424_F −0.18 0.205 0.43 460 PGF_E33_F −0.12 0.207 0.43 461 VAV1_E9_F −0.10 0.207 0.43 462 KDR_E79_F −0.13 0.207 0.43 463 ASB4_P52_R −0.16 0.208 0.43 464 IGF1R_E186_R −0.13 0.208 0.43 465 PWCR1_P357_F 0.06 0.208 0.43 466 PTEN_P438_F −0.16 0.210 0.43 467 XRCC2_P1077_F −0.12 0.210 0.43 468 APBA2_P305_R −0.09 0.211 0.43 469 DSC2_E90_F −0.12 0.211 0.43 470 IAPP_E280_F −0.11 0.212 0.43 471 FANCG_E207_R −0.18 0.212 0.43 472 NOS2A_P288_R −0.09 0.214 0.43 473 INHA_P1144_R −0.08 0.215 0.43 474 EPHA1_E46_R −0.23 0.215 0.43 475 CCND2_P887_F −0.15 0.216 0.43 476 SPI1_E205_F −0.14 0.217 0.43 477 PTHR1_E36_R −0.12 0.217 0.43 478 GPR116_E328_R −0.14 0.217 0.43 479 BMPR1A_P956_F −0.16 0.218 0.43 480 NFKB2_P709_R −0.17 0.219 0.43 481 ID1_P659_R 0.16 0.219 0.43 482 H19_P541_F −0.35 0.220 0.43 483 PDGFRB_P273_F 0.09 0.220 0.43 484 ZP3_E90_F 0.15 0.220 0.43 485 PLAGL1_P334_F 0.07 0.220 0.43 486 TFF2_P557_R −0.12 0.220 0.43 487 UGT1A1_P315_R −0.08 0.220 0.43 488 PTK7_E317_F −0.06 0.221 0.43 489 S100A2_P1186_F −0.08 0.221 0.43 490 MBD2_P233_F −0.07 0.222 0.43 491 IL12A_E287_R −0.08 0.224 0.43 492 DSP_P36_F −0.09 0.225 0.43 493 SOX1_P294_F −0.10 0.226 0.43 494 SLC22A2_P109_F −0.07 0.226 0.43 495 UGT1A1_P564_R −0.07 0.227 0.43 496 COL1A1_P117_R −0.09 0.227 0.43 497 LRRK1_P39_F −0.10 0.227 0.43 498 HLA-DOB_E432_R −0.08 0.228 0.43 499 DNMT1_P100_R −0.17 0.228 0.43 500 NQO1_P345_R 0.12 0.228 0.43 501 HLA-DOB_P1114_R −0.11 0.230 0.43 502 LEFTY2_P719_F −0.10 0.230 0.43 503 HLA-DOB_P357_R −0.13 0.230 0.43 504 PTGS2_P308_F −0.20 0.230 0.43 505 GABRA5_P1016_F −0.08 0.230 0.43 506 HHIP_E94_F −0.13 0.230 0.43 507 MALT1_P406_R −0.17 0.231 0.43 508 ABCB4_P51_F −0.11 0.233 0.43 509 LCK_E28_F −0.07 0.234 0.43 510 IL1RN_P93_R −0.08 0.234 0.43 511 CXCL9_E268_R −0.10 0.234 0.43 512 DSP_P440_R −0.23 0.234 0.43 513 TIMP3_P1114_R −0.12 0.234 0.43 514 IMPACT_P186_F −0.22 0.234 0.43 515 IHH_P246_R −0.08 0.234 0.43 516 CARD15_P302_R 0.16 0.234 0.43 517 SLC5A8_P38_R −0.10 0.234 0.43 518 CPA4_E20_F −0.10 0.235 0.43 519 DIO3_P674_F 0.14 0.235 0.43 520 IFNGR1_P307_F −0.13 0.235 0.43 521 EIF2AK2_P313_F −0.25 0.235 0.43 522 ERBB4_P541_F −0.13 0.236 0.43 523 E2F3_P840_R −0.12 0.237 0.43 524 TIMP3_P690_R −0.10 0.238 0.43 525 SLC22A2_E271_R −0.10 0.238 0.43 526 CDKN1A_P242_F 0.20 0.239 0.43 527 CSTB_E410_F 0.12 0.240 0.43 528 GUCY2D_P48_R −0.09 0.240 0.43 529 JAK3_E64_F −0.10 0.241 0.43 530 EXT1_E197_F −0.12 0.242 0.43 531 VAV2_P1182_F 0.21 0.242 0.43 532 HRA5LS_E72_R −0.15 0.243 0.44 533 DAPK1_P345_R −0.20 0.244 0.44 534 JAG2_E54_F −0.09 0.245 0.44 535 HCK_P46_R −0.12 0.245 0.44 536 TNFRSF10D_E27_F 0.16 0.246 0.44 537 MSH3_E3_F −0.33 0.246 0.44 538 TSG101_P257_R −0.12 0.248 0.44 539 LIG3_P622_R −0.06 0.248 0.44 540 MSH3_P13_R −0.21 0.248 0.44 541 SERPINB5_P19_R −0.11 0.249 0.44 542 SMO_P455_R −0.11 0.250 0.44 543 DLL1_P386_F 0.23 0.254 0.45 544 CDC25B_E83_F −0.14 0.255 0.45 545 FRK_P258_F −0.13 0.255 0.45 546 WNT8B_P216_R −0.12 0.256 0.45 547 CD1A_P6_F −0.07 0.258 0.45 548 SPI1_P929_F −0.06 0.260 0.45 549 GAS1_P754_R −0.14 0.260 0.45 550 DSG1_P159_R −0.09 0.261 0.45 551 PMP22_P1254_F −0.09 0.261 0.45 552 CASP10_P186_F −0.11 0.261 0.45 553 AXL_E61_F −0.11 0.262 0.45 554 S100A12_P1221_R −0.04 0.264 0.45 555 SGCE_E149_F −0.12 0.267 0.46 556 EPHA3_P106_R −0.16 0.268 0.46 557 CTSL_P81_F 0.11 0.268 0.46 558 CSF1_P217_F −0.18 0.269 0.46 559 RET_P717_F −0.11 0.269 0.46 560 FYN_P352_R −0.10 0.270 0.46 561 OSM_P34_F −0.09 0.272 0.46 562 BIRC5_E89_F 0.45 0.272 0.46 563 IL2_P607_R −0.09 0.272 0.46 564 UNG_P170_F 0.15 0.273 0.46 565 MYH11_P236_R −0.21 0.273 0.46 566 DIRAS3_E55_R −0.08 0.273 0.46 567 RIPK1_P744_R −0.11 0.274 0.46 568 CDH17_P532_F −0.09 0.274 0.46 569 CDK2_P330_R 0.14 0.275 0.46 570 WNT5A_E43_F −0.09 0.276 0.46 571 NOTCH3_P198_R −0.09 0.277 0.46 572 MTA1_P478_F −0.12 0.277 0.46 573 VAV2_E58_F 0.09 0.277 0.46 574 FAT_P973_R −0.15 0.278 0.46 575 GPX3_E178_F −0.05 0.278 0.46 576 HTR1B_E232_R −0.08 0.280 0.46 577 GNMT_E126_F 0.13 0.282 0.46 578 DNMT3B_P352_R −0.08 0.282 0.46 579 CAV1_P130_R −0.09 0.282 0.47 580 SMAD2_P708_R −0.07 0.284 0.47 581 KCNQ1_E349_R −0.10 0.284 0.47 582 C20orf47_P225_R −0.10 0.285 0.47 583 KLK11_P103_R −0.07 0.285 0.47 584 PYCARD_E87_F −0.10 0.286 0.47 585 HPN_P374_R −0.16 0.286 0.47 586 ACTG2_E98_R −0.13 0.287 0.47 587 HLA-DPB1_P540_F −0.08 0.287 0.47 588 TDG_E129_F −0.10 0.288 0.47 589 DCN_P1320_R −0.10 0.289 0.47 590 CRIP1_P874_R −0.10 0.292 0.47 591 NOS3_P38_F −0.05 0.293 0.47 592 GALR1_E52_F −0.11 0.295 0.47 593 DSG1_E292_F −0.05 0.295 0.47 594 EVI1_E47_R −0.16 0.296 0.47 595 SNCG_E119_F −0.09 0.296 0.47 596 EPS8_P437_F −0.11 0.297 0.47 597 HOXC6_P585_R 0.08 0.299 0.47 598 IGF2R_P396_R −0.06 0.300 0.47 599 ITPR3_P1112_F −0.14 0.300 0.47 600 SEMA3A_P658_R −0.11 0.301 0.47 601 FGF6_E294_F −0.08 0.302 0.47 602 MMP1_P460_F −0.08 0.302 0.47 603 TIAM1_P117_F −0.15 0.302 0.47 604 GFAP_P1214_F −0.05 0.302 0.47 605 SERPINB2_P939_F −0.11 0.302 0.47 606 P2RX7_P119_R −0.11 0.303 0.47 607 SNCG_P53_F −0.12 0.303 0.47 608 IL3_P556_F −0.09 0.303 0.47 609 MPO_E302_R 0.07 0.303 0.47 610 TBX1_P885_R −0.09 0.304 0.47 611 EFNA1_P591_R −0.18 0.304 0.47 612 FGF12_P210_R −0.12 0.304 0.47 613 FZD9_P15_R −0.18 0.305 0.47 614 CDC25B_P11_R −0.11 0.305 0.47 615 ADAMTS12_P250_R −0.12 0.306 0.47 616 IL12B_P1453_F −0.06 0.306 0.47 617 IGFBP2_P353_R −0.10 0.307 0.47 618 HBII-52_P659_F −0.08 0.307 0.47 619 CDH11_E102_R −0.11 0.307 0.47 620 CDH3_P87_R −0.18 0.307 0.47 621 NID1_P677_F −0.09 0.308 0.47 622 P2RX7_E323_R −0.09 0.309 0.47 623 PYCARD_P150_F −0.08 0.309 0.47 624 IGF2AS_E4_F −0.05 0.309 0.47 625 TNFRSF10A_P91_F −0.11 0.310 0.47 626 KIT_P405_F −0.07 0.310 0.47 627 WNT5A_P655_F −0.15 0.311 0.47 628 MMP14_P13_F 0.09 0.311 0.47 629 TMEFF1_P234_F −0.12 0.312 0.47 630 DAPK1_P10_F −0.09 0.312 0.47 631 GSTP1_P74_F 0.08 0.314 0.47 632 TNFSF10_P2_R −0.17 0.314 0.47 633 SKI_E465_R −0.09 0.314 0.47 634 TUBB3_P364_F −0.12 0.315 0.47 635 LY6G6E_P45_R −0.08 0.316 0.47 636 ENC1_P484_R −0.06 0.316 0.47 637 TIE1_E66_R 0.12 0.316 0.47 638 CCNA1_E7_F −0.22 0.317 0.47 639 GABRG3_E123_R −0.07 0.317 0.47 640 PI3_P1394_R −0.05 0.317 0.47 641 ARHGDIB_P148_R −0.07 0.318 0.47 642 SERPINA5_E69_F −0.07 0.318 0.47 643 FASTK_P598_R −0.05 0.318 0.47 644 TNC_P198_F −0.12 0.319 0.47 645 BCAM_P205_F −0.10 0.320 0.47 646 WNT10B_P993_F −0.11 0.320 0.47 647 MLF1_E243_F −0.05 0.320 0.47 648 ETS2_P684_F −0.12 0.320 0.47 649 ALOX12_E85_R 0.20 0.320 0.47 650 FGR_P39_F −0.09 0.324 0.47 651 BCAM_E100_R −0.07 0.324 0.47 652 GJB2_P791_R −0.08 0.325 0.47 653 ELL_P693_F −0.10 0.325 0.47 654 THY1_P149_R −0.09 0.326 0.47 655 GPR116_P850_F −0.09 0.326 0.47 656 RIPK3_P124_F −0.12 0.326 0.47 657 HLA-DOA_P594_F −0.07 0.326 0.47 658 PDE1B_P263_R −0.08 0.326 0.47 659 NEO1_P1067_F −0.16 0.327 0.47 660 DDR2_E331_F −0.09 0.329 0.47 661 ACTG2_P346_F −0.06 0.330 0.47 662 CLDN4_P1120_R −0.05 0.330 0.47 663 RARA_E128_R −0.09 0.331 0.47 664 TRPM5_P721_F −0.09 0.331 0.47 665 CD9_P504_F −0.11 0.331 0.47 666 NDN_P1110_F −0.09 0.332 0.47 667 PLG_E406_F −0.09 0.332 0.47 668 CTGF_P693_R −0.11 0.332 0.47 669 NTSR1_E109_F 0.13 0.332 0.47 670 CD9_P585_R −0.07 0.333 0.47 671 TP73_P945_F −0.07 0.334 0.47 672 MMP2_P197_F −0.08 0.335 0.47 673 ITGA6_P718_R −0.07 0.336 0.47 674 ASB4_E89_F −0.08 0.337 0.47 675 ASCL1_P747_F −0.06 0.337 0.47 676 CREB1_P819_F −0.19 0.337 0.47 677 POMC_P400_R −0.20 0.337 0.47 678 NGFB_E353_F −0.08 0.339 0.48 679 ACVR1_P983_F −0.06 0.339 0.48 680 EPHB3_P569_R 0.10 0.339 0.48 681 HOXB2_P99_F 0.07 0.339 0.48 682 TNFRSF10C_P612_R −0.44 0.340 0.48 683 ARNT_P238_R −0.13 0.340 0.48 684 KRT5_E196_R −0.07 0.341 0.48 685 MOS_P746_F −0.10 0.341 0.48 686 SEPT9_P58_R −0.07 0.343 0.48 687 HLA-DQA2_E93_F −0.05 0.343 0.48 688 AFP_P824_F −0.08 0.343 0.48 689 ACVR1B_P572_R −0.10 0.343 0.48 690 JAG1_P66_F −0.07 0.344 0.48 691 PWCR1_P811_F −0.06 0.345 0.48 692 NBL1_P24_F −0.08 0.346 0.48 693 RARRES1_P57_R −0.03 0.346 0.48 694 CPA4_P1265_R −0.10 0.349 0.48 695 MMP9_E88_R −0.06 0.350 0.48 696 ERCC3_P1210_R 0.09 0.351 0.48 697 GSTM1_P363_F 0.18 0.351 0.48 698 RARB_P60_F −0.08 0.354 0.48 699 PMP22_P975_F −0.08 0.354 0.48 700 DNAJC15_E26_R −0.08 0.354 0.48 701 TUBB3_P721_R 0.10 0.355 0.48 702 FANCA_P1006_R −0.08 0.356 0.48 703 KLK11_P1290_F −0.06 0.358 0.49 704 NRG1_P558_R 0.11 0.359 0.49 705 CTSL_P264_R −0.06 0.359 0.49 706 SNCG_P98_R −0.05 0.359 0.49 707 CDH1_P45_F −0.09 0.360 0.49 708 TRIM29_P261_F −0.08 0.360 0.49 709 IGFBP7_P371_F 0.10 0.361 0.49 710 LIMK1_P709_R −0.07 0.361 0.49 711 NOTCH2_P312_R −0.06 0.363 0.49 712 APBA2_P227_F −0.07 0.364 0.49 713 LYN_P241_F −0.07 0.364 0.49 714 NTRK1_E74_F 0.42 0.365 0.49 715 UBA52_P293_R −0.16 0.366 0.49 716 UGT1A7_P751_R −0.08 0.366 0.49 717 HS3ST2_P171_F −0.07 0.366 0.49 718 HTR2A_P853_F −0.11 0.367 0.49 719 SFN_P248_F −0.11 0.368 0.49 720 BCL2L2_E172_F 0.19 0.370 0.49 721 LMO2_P794_R 0.14 0.370 0.49 722 PTPNS1_P301_R −0.07 0.371 0.49 723 IRF7_P277_R −0.09 0.372 0.49 724 GFAP_P56_R −0.06 0.372 0.49 725 FASTK_P257_F 0.08 0.373 0.49 726 ALK_P28_F −0.06 0.373 0.49 727 SPP1_P647_F −0.09 0.373 0.49 728 NCL_P840_R −0.10 0.373 0.49 729 RBP1_P426_R −0.08 0.375 0.49 730 EPHB6_E342_F 0.09 0.376 0.49 731 CHI3L2_E10_F −0.05 0.376 0.49 732 EPHB4_E476_R −0.07 0.377 0.49 733 KLF5_E190_R −0.06 0.378 0.49 734 PLA2G2A_P528_F −0.05 0.378 0.49 735 LRRC32_P865_R −0.09 0.378 0.49 736 MGMT_P272_R −0.09 0.379 0.49 737 COL6A1_P425_F −0.04 0.379 0.49 738 PRSS8_E134_R −0.08 0.382 0.49 739 PTPRO_E56_F 0.07 0.383 0.49 740 GFI1_E136_F 0.11 0.384 0.49 741 CDH3_E100_R −0.07 0.384 0.49 742 DLL1_P832_F −0.13 0.384 0.49 743 SLC22A3_E122_R −0.15 0.387 0.49 744 GALR1_P80_F −0.08 0.387 0.49 745 HOXC6_P456_R −0.08 0.387 0.49 746 SMAD2_P848_R −0.08 0.388 0.49 747 HOXB13_P17_R −0.07 0.388 0.49 748 HOXB2_P488_R −0.05 0.389 0.49 749 MMP2_E21_R −0.10 0.389 0.49 750 NGFR_E328_F −0.09 0.389 0.49 751 GP1BB_P278_R 0.08 0.390 0.49 752 MAP3K9_E17_R −0.12 0.390 0.49 753 DDB2_P407_F −0.07 0.390 0.49 754 RARRES1_E235_F −0.05 0.391 0.49 755 WNT10B_P823_R −0.09 0.391 0.49 756 MATK_P64_F −0.09 0.391 0.49 757 TDGF1_P428_R −0.08 0.391 0.49 758 HCK_P858_F −0.12 0.392 0.49 759 AGXT_E115_R −0.08 0.393 0.49 760 BAX_E281_R −0.05 0.393 0.49 761 GSTM2_E153_F −0.08 0.394 0.49 762 ITGA2_E120_F −0.07 0.394 0.49 763 IL18BP_P51_R −0.09 0.395 0.49 764 RARB_E114_F −0.07 0.395 0.49 765 GAS7_P622_R −0.10 0.395 0.49 766 AHR_E103_F 0.07 0.396 0.49 767 EDNRB_P709_R −0.08 0.396 0.49 768 IMPACT_P234_R 0.15 0.397 0.49 769 FAT_P279_R −0.08 0.397 0.49 770 PGR_P456_R −0.07 0.397 0.49 771 PTGS2_P524_R −0.10 0.399 0.49 772 EPHA2_P203_F 0.08 0.400 0.49 773 KRAS_P651_F −0.04 0.401 0.49 774 DAPK1_E46_R 0.08 0.402 0.49 775 MKRN3_P108_F −0.09 0.402 0.49 776 PITX2_E24_R 0.12 0.403 0.49 777 CD86_P3_F −0.09 0.403 0.49 778 PLSCR3_P751_R −0.06 0.403 0.49 779 LAMC1_P808_F −0.07 0.404 0.49 780 PRKAR1A_P337_R −0.13 0.404 0.49 781 SFTPA1_P421_F −0.09 0.405 0.49 782 GDF10_P95_R −0.05 0.406 0.50 783 TGFBR3_E188_R −0.09 0.409 0.50 784 HGF_P1293_R −0.07 0.409 0.50 785 PDGFRA_E125_F −0.09 0.409 0.50 786 PLAUR_E123_F 0.06 0.410 0.50 787 NRAS_P103_R −0.14 0.412 0.50 788 MOS_P27_R 0.13 0.413 0.50 789 RBP1_P150_F −0.12 0.414 0.50 790 PRDM2_P1340_R −0.07 0.414 0.50 791 CD34_P780_R −0.07 0.415 0.50 792 PTCH2_E173_F −0.04 0.416 0.50 793 CSF1_P339_F −0.09 0.417 0.50 794 TGFB3_E58_R −0.06 0.417 0.50 795 TCF7L2_E411_F −0.10 0.418 0.50 796 CYP1B1_P212_F −0.04 0.418 0.50 797 KRAS_E82_F 0.08 0.418 0.50 798 PTPRF_E178_R 0.11 0.419 0.50 799 SNRPN_P230_R −0.06 0.419 0.50 800 CHFR_P501_F −0.11 0.419 0.50 801 ASB4_P391_F −0.07 0.420 0.50 802 DLC1_E276_F −0.08 0.421 0.50 803 KIT_P367_R −0.09 0.421 0.50 804 CDKN2A_E121_R −0.07 0.422 0.50 805 BMPR2_P1271_F −0.11 0.422 0.50 806 MYBL2_P211_F −0.12 0.423 0.50 807 CEACAM1_P44_R −0.06 0.423 0.50 808 PLAU_P11_F −0.08 0.424 0.50 809 TJP1_P390_F −0.06 0.424 0.50 810 TPEF_seq_44_S36_F −0.05 0.425 0.50 811 MAGEL2_E166_R −0.08 0.425 0.50 812 OGG1_E400_F 0.07 0.427 0.50 813 ITPR3_E86_R −0.15 0.428 0.50 814 TGFA_P642_R −0.11 0.428 0.50 815 EGFR_E295_R −0.08 0.428 0.50 816 ERN1_P809_R 0.05 0.429 0.50 817 IL12B_E25_F −0.05 0.429 0.50 818 HLA-DPA1_P28_R 0.08 0.430 0.50 819 IGF2_P1036_R 0.06 0.431 0.50 820 HOXA11_P698_F −0.15 0.431 0.50 821 WNT2B_P1185_R −0.11 0.432 0.50 822 KCNK4_P171_R −0.09 0.432 0.50 823 GRB7_E71_R −0.07 0.433 0.50 824 GFI1_P45_R −0.08 0.434 0.50 825 HDAC7A_P344_F −0.06 0.434 0.50 826 EPHA5_P66_F −0.07 0.434 0.50 827 AIM2_P624_F −0.09 0.434 0.50 828 MMP9_P237_R −0.09 0.434 0.50 829 MYCN_P464_R −0.05 0.435 0.50 830 MXI1_P1269_F −0.07 0.435 0.50 831 TEK_P479_R −0.05 0.436 0.50 832 DMP1_E194_F −0.05 0.436 0.50 833 PLAT_P80_F −0.09 0.439 0.50 834 CFTR_P372_R 0.07 0.440 0.50 835 CCL3_P543_R −0.07 0.440 0.50 836 HHIP_P307_R −0.05 0.441 0.50 837 SHH_E328_F −0.07 0.443 0.51 838 TUSC3_P85_R 0.08 0.444 0.51 839 DAB2_P35_F −0.07 0.445 0.51 840 TESK2_P252_R −0.06 0.445 0.51 841 PLXDC2_P914_R −0.08 0.445 0.51 842 MMP14_P208_R −0.07 0.446 0.51 843 PDGFRB_E195_R −0.06 0.446 0.51 844 FZD9_P175_F −0.05 0.447 0.51 845 IHH_P529_F −0.09 0.449 0.51 846 SOX17_P287_R −0.07 0.450 0.51 847 MCM6_E136_F −0.09 0.450 0.51 848 CHGA_P243_F −0.08 0.451 0.51 849 ESR1_E298_R −0.10 0.453 0.51 850 SRC_P297_F −0.09 0.454 0.51 851 MMP2_P303_R −0.07 0.455 0.51 852 TNFSF8_P184_F −0.08 0.455 0.51 853 CSF3R_P8_F −0.06 0.456 0.51 854 CD2_P68_F −0.08 0.458 0.51 855 CDK10_P199_R −0.06 0.458 0.51 856 GRB10_P260_F −0.09 0.462 0.52 857 ZNF264_P397_F −0.10 0.465 0.52 858 BCR_P422_F −0.05 0.466 0.52 859 JAK3_P1075_R −0.05 0.467 0.52 860 PDGFA_P78_F −0.05 0.468 0.52 861 SOD3_P225_F −0.07 0.469 0.52 862 HLA-DPA1_E35_R 0.06 0.469 0.52 863 MAP3K8_P1036_F 0.07 0.473 0.52 864 HTR1B_P107_F −0.04 0.473 0.52 865 GNAS_E58_F 0.08 0.474 0.52 866 NOTCH1_P1198_F 0.11 0.474 0.52 867 C4B_E171_F −0.05 0.474 0.52 868 SLC22A3_P634_F −0.07 0.475 0.52 869 GABRA5_E44_R −0.06 0.477 0.52 870 PTPRH_P255_F −0.05 0.478 0.52 871 SPARC_E50_R −0.03 0.479 0.52 872 DNMT2_P199_F −0.04 0.480 0.52 873 SMAD4_P474_R −0.08 0.480 0.52 874 PPAT_E170_R 0.06 0.480 0.52 875 SLC22A18_P216_R 0.07 0.480 0.52 876 SRC_P164_F −0.04 0.481 0.52 877 MMP19_E274_R −0.04 0.482 0.52 878 IGSF4C_P533_R 0.07 0.482 0.52 879 SNURF_P78_F 0.05 0.483 0.52 880 GATA6_P726_F −0.07 0.485 0.52 881 ASCL2_E76_R −0.06 0.486 0.52 882 AFF3_P808_F −0.06 0.486 0.52 883 SERPINE1_E189_R −0.05 0.489 0.52 884 UGT1A1_E11_F −0.06 0.489 0.52 885 PLA2G2A_E268_F −0.05 0.489 0.52 886 IL1B_P582_R −0.04 0.489 0.52 887 CDKN1A_E101_F 0.06 0.490 0.52 888 HBII-13_E48_F −0.07 0.490 0.52 889 MOS_E60_R 0.10 0.491 0.52 890 RUNX3_P247_F −0.07 0.491 0.52 891 HBII-13_P991_R 0.05 0.491 0.52 892 SHB_P473_R 0.06 0.491 0.52 893 TRIM29_P135_F −0.04 0.491 0.52 894 MSH2_P1008_F 0.05 0.492 0.53 895 ZMYND10_P329_F −0.07 0.493 0.53 896 SH3BP2_E18_F −0.08 0.494 0.53 897 ERCC6_P698_R −0.05 0.495 0.53 898 ALOX12_P223_R 0.15 0.496 0.53 899 C4B_P191_F −0.08 0.497 0.53 900 TFPI2_P152_R −0.06 0.498 0.53 901 TNF_P158_F −0.13 0.498 0.53 902 GJB2_E43_F 0.13 0.501 0.53 903 SLC22A3_P528_F −0.06 0.501 0.53 904 BMP4_P199_R 0.07 0.501 0.53 905 TUBB3_E91_F −0.17 0.503 0.53 906 ITGB1_P451_F −0.05 0.503 0.53 907 LOX_P313_R −0.08 0.504 0.53 908 SLIT2_E111_R −0.04 0.504 0.53 909 AATK_E63_R −0.06 0.504 0.53 910 APOC1_P406_R −0.02 0.507 0.53 911 TES_E172_F −0.07 0.508 0.53 912 CALCA_P171_F −0.04 0.511 0.53 913 FGFR2_P266_R −0.06 0.511 0.53 914 NEFL_E23_R 0.12 0.511 0.53 915 CCNE1_P683_F −0.03 0.512 0.53 916 CYP2E1_E53_R −0.06 0.515 0.54 917 AATK_P709_R 0.08 0.516 0.54 918 ISL1_P554_F −0.10 0.516 0.54 919 IL1A_E113_R −0.06 0.516 0.54 920 SOD3_P460_R −0.05 0.517 0.54 921 DHCR24_P406_R −0.08 0.517 0.54 922 CPA4_P961_R 0.03 0.518 0.54 923 MME_E29_F −0.11 0.519 0.54 924 CASP10_P334_F −0.08 0.519 0.54 925 USP29_P205_R −0.03 0.522 0.54 926 TP73_P496_F 0.07 0.523 0.54 927 IL6_P213_R −0.08 0.523 0.54 928 GNAS_P86_F −0.04 0.523 0.54 929 PYCARD_P393_F 0.04 0.524 0.54 930 NRAS_P12_R −0.11 0.525 0.54 931 ABL1_P53_F −0.10 0.526 0.54 932 FN1_E469_F −0.07 0.526 0.54 933 TYK2_P494_F −0.07 0.527 0.54 934 S100A4_P194_R −0.05 0.527 0.54 935 ST6GAL1_P528_F 0.12 0.529 0.54 936 DST_P262_R −0.07 0.532 0.54 937 AGTR1_P41_F 0.10 0.532 0.54 938 LAMC1_E466_R −0.08 0.532 0.54 939 EYA4_E277_F −0.10 0.532 0.54 940 HOXA9_E252_R 0.07 0.532 0.54 941 GADD45A_P737_R 0.05 0.533 0.54 942 ONECUT2_P315_R −0.10 0.535 0.54 943 MLLT3_E93_R −0.04 0.535 0.54 944 SEZ6L_P299_F −0.09 0.536 0.54 945 NFKB1_P336_R 0.19 0.537 0.54 946 HLA-DQA2_P282_R −0.06 0.538 0.54 947 PTHR1_P170_R −0.05 0.541 0.55 948 JAK2_P772_R −0.08 0.542 0.55 949 CYP2E1_P416_F −0.06 0.543 0.55 950 HOXA5_P479_F −0.05 0.545 0.55 951 FLT3_E326_R 0.09 0.546 0.55 952 ABO_E110_F −0.05 0.547 0.55 953 THY1_P20_R −0.03 0.547 0.55 954 SNRPN_seq_18_S99_F 0.03 0.553 0.55 955 WNT8B_E487_F −0.04 0.553 0.55 956 GLI3_P453_R 0.07 0.555 0.55 957 WT1_E32_F 0.07 0.555 0.55 958 IL10_P348_F 0.08 0.556 0.55 959 RAF1_P330_F −0.06 0.557 0.55 960 PAX6_P50_R −0.05 0.559 0.56 961 NTSR1_P318_F −0.06 0.560 0.56 962 PCDH1_P264_F −0.12 0.562 0.56 963 FRZB_E186_R −0.05 0.562 0.56 964 ETS1_P559_R −0.06 0.564 0.56 965 MEST_P62_R −0.08 0.564 0.56 966 STAT5A_E42_F −0.04 0.566 0.56 967 TFF2_P178_F −0.03 0.570 0.56 968 TRPM5_P979_F −0.03 0.572 0.56 969 ZIM3_P451_R −0.05 0.572 0.56 970 LRP2_E20_F −0.03 0.573 0.56 971 NBL1_E205_R −0.05 0.573 0.56 972 BDNF_P259_R −0.05 0.575 0.56 973 EPM2A_P113_F −0.07 0.576 0.56 974 LAMB1_E144_R −0.03 0.577 0.57 975 LTA_P214_R −0.05 0.578 0.57 976 NEFL_P209_R −0.07 0.579 0.57 977 MAPK10_E26_F −0.03 0.579 0.57 978 ARHGAP9_P518_R −0.04 0.581 0.57 979 ROR2_P317_R 0.06 0.582 0.57 980 ABCB4_P892_F −0.20 0.583 0.57 981 PDGFRA_P1429_F −0.09 0.583 0.57 982 IRF7_E236_R −0.04 0.584 0.57 983 p16_seq_47_S188_R −0.06 0.585 0.57 984 ABCC2_E16_R 0.16 0.585 0.57 985 ICAM1_P119_R −0.07 0.586 0.57 986 DAB2IP_P9_F −0.08 0.586 0.57 987 HGF_E102_R −0.07 0.587 0.57 988 COL1A2_E299_F −0.05 0.587 0.57 989 GML_E144_F 0.19 0.587 0.57 990 LOX_P71_F −0.07 0.588 0.57 991 HLA-DOA_P191_R −0.07 0.590 0.57 992 MAP2K6_P297_R 0.04 0.592 0.57 993 IL8_P83_F −0.06 0.593 0.57 994 TGFB2_E226_R −0.07 0.595 0.57 995 COL1A2_P407_R 0.04 0.596 0.57 996 TCF7L2_P193_R 0.08 0.596 0.57 997 NR2F6_E375_R −0.03 0.597 0.57 998 GSTP1_seq_38_S153 −0.05 0.597 0.57 999 ZNF215_P71_R 0.04 0.597 0.57 1000 PTK2B_P673_R 0.06 0.598 0.57 1001 FES_E34_R 0.04 0.598 0.57 1002 LYN_E353_F 0.07 0.599 0.57 1003 TCF4_P175_R 0.11 0.601 0.57 1004 YES1_P600_F −0.08 0.603 0.57 1005 TRIM29_E189_F −0.03 0.604 0.57 1006 THBS1_E207_R 0.05 0.604 0.57 1007 NPY_P295_F −0.06 0.607 0.57 1008 GRB10_P496_R −0.06 0.607 0.57 1009 PI3_E107_F −0.12 0.608 0.57 1010 NGFB_P13_F −0.03 0.608 0.57 1011 TYRO3_P366_F −0.06 0.609 0.57 1012 CSF2_P605_F −0.03 0.609 0.57 1013 PLG_P370_F −0.02 0.613 0.58 1014 TIAM1_P188_R 0.07 0.613 0.58 1015 IHH_E186_F 0.07 0.614 0.58 1016 IGFBP5_P9_R 0.06 0.615 0.58 1017 SFTPD_E169_F −0.03 0.617 0.58 1018 DAB2_P468_F −0.07 0.617 0.58 1019 MMP8_E89_R 0.05 0.617 0.58 1020 CAV2_E33_R 0.08 0.619 0.58 1021 RAN_P581_R −0.04 0.622 0.58 1022 SEPT5_P441_F −0.04 0.625 0.58 1023 TUSC3_E29_R −0.07 0.627 0.58 1024 BMP6_P398_F −0.03 0.627 0.58 1025 TGFBI_P31_R 0.05 0.627 0.58 1026 MYCL1_P502_R −0.06 0.629 0.58 1027 RIPK3_P24_F −0.08 0.629 0.58 1028 TM7SF3_P1068_R 0.05 0.630 0.58 1029 ITGA2_P26_R 0.07 0.630 0.58 1030 CARD15_P665_F −0.05 0.630 0.58 1031 ACVR2B_P676_F −0.06 0.630 0.58 1032 PECAM1_P135_F −0.06 0.631 0.58 1033 PLXDC2_E337_F 0.07 0.631 0.58 1034 RASGRF1_P768_F −0.08 0.632 0.58 1035 EPHB4_P313_R −0.07 0.633 0.58 1036 ERCC1_P440_R −0.05 0.634 0.58 1037 HS3ST2_E145_R 0.05 0.635 0.58 1038 EPHX1_P22_F −0.03 0.635 0.58 1039 MFAP4_P197_F −0.06 0.635 0.58 1040 PTGS1_E80_F −0.03 0.637 0.58 1041 THPO_E483_F 0.03 0.637 0.58 1042 CCKAR_E79_F −0.04 0.638 0.58 1043 FANCF_P13_F −0.07 0.638 0.58 1044 THBS2_E129_F 0.07 0.639 0.58 1045 GLI3_E148_R 0.03 0.639 0.58 1046 SFTPC_E13_F 0.04 0.640 0.58 1047 TFRC_P414_R 0.05 0.641 0.58 1048 SNRPN_E14_F −0.02 0.642 0.58 1049 FES_P223_R −0.05 0.643 0.58 1050 PTGS1_P2_F −0.04 0.643 0.58 1051 CDH13_P88_F −0.06 0.644 0.58 1052 PPARG_P693_F −0.05 0.644 0.58 1053 PPARG_E178_R 0.05 0.644 0.58 1054 TNFRSF1A_P678_F −0.04 0.644 0.58 1055 DCC_E53_R 0.05 0.646 0.58 1056 ADCYAP1_P455_R −0.04 0.647 0.58 1057 HPN_P823_F −0.06 0.649 0.59 1058 MLLT6_P957_F −0.04 0.650 0.59 1059 TMPRSS4_P552_F −0.04 0.652 0.59 1060 CASP6_P201_F −0.04 0.652 0.59 1061 FGF6_P139_R −0.04 0.653 0.59 1062 IL6_P611_F −0.05 0.653 0.59 1063 NOTCH1_E452_R −0.08 0.654 0.59 1064 AATK_P519_R 0.03 0.655 0.59 1065 ESR2_E66_F −0.07 0.658 0.59 1066 IGSF4C_E65_F −0.03 0.660 0.59 1067 APBA1_P644_F −0.05 0.660 0.59 1068 HTR1B_P222_F −0.06 0.661 0.59 1069 GPATC3_P410_R −0.04 0.661 0.59 1070 IGF2_P36_R −0.08 0.662 0.59 1071 CHFR_P635_R −0.02 0.662 0.59 1072 HDAC5_E298_F −0.02 0.663 0.59 1073 IGF1R_P325_R −0.04 0.663 0.59 1074 GSTM1_P266_F 0.12 0.664 0.59 1075 PSIP1_P163_R −0.05 0.664 0.59 1076 PTPRG_P476_F −0.05 0.664 0.59 1077 BCL3_E71_F −0.02 0.665 0.59 1078 MLF1_P97_F −0.04 0.666 0.59 1079 EPHB2_P165_R 0.09 0.666 0.59 1080 TFF1_P180_R −0.02 0.667 0.59 1081 RARA_P1076_R −0.05 0.668 0.59 1082 WRN_E57_F −0.06 0.668 0.59 1083 POMC_P53_F −0.04 0.669 0.59 1084 NPY_P91_F −0.04 0.670 0.59 1085 TIMP3_seq_7_S38_F −0.04 0.671 0.59 1086 SPI1_P48_F −0.05 0.671 0.59 1087 FGF7_P610_F −0.03 0.671 0.59 1088 CSF3_P309_R −0.04 0.672 0.59 1089 MST1R_E42_R −0.03 0.672 0.59 1090 TERT_E20_F 0.03 0.673 0.59 1091 HOXA9_P1141_R −0.04 0.674 0.59 1092 MFAP4_P10_R −0.02 0.674 0.59 1093 PTPRO_P371_F 0.04 0.676 0.59 1094 EYA4_P508_F −0.06 0.677 0.59 1095 MAPK12_P416_F −0.06 0.678 0.59 1096 PDGFB_E25_R 0.04 0.679 0.59 1097 ALPL_P433_F −0.03 0.679 0.59 1098 APC_P280_R −0.05 0.681 0.59 1099 EPM2A_P64_R 0.05 0.681 0.59 1100 PLAU_P176_R 0.09 0.683 0.59 1101 EPHA1_P119_R 0.04 0.683 0.59 1102 SYK_P584_F 0.04 0.684 0.59 1103 EPHX1_E152_F −0.02 0.684 0.59 1104 LMO1_P169_F −0.08 0.684 0.59 1105 BRCA1_P835_R −0.05 0.684 0.59 1106 ARHGAP9_P260_F −0.03 0.684 0.59 1107 BMPR2_E435_F −0.06 0.686 0.59 1108 TGFBI_P173_F −0.04 0.686 0.59 1109 CCKBR_P480_F 0.03 0.686 0.59 1110 EPHA2_P340_R 0.04 0.687 0.59 1111 FLT1_P615_R −0.05 0.688 0.59 1112 SNRPN_seq_12_S12$$ −0.02 0.688 0.59 1113 BDNF_E19_R −0.04 0.689 0.59 1114 TWIST1_P355_R −0.05 0.689 0.59 1115 GML_P281_R −0.03 0.691 0.59 1116 APC_E117_R 0.02 0.692 0.59 1117 HTR2A_E10_R −0.02 0.693 0.59 1118 MC2R_E455_F −0.03 0.693 0.59 1119 SLIT2_P208_F −0.05 0.693 0.59 1120 IRF5_P123_F −0.02 0.695 0.59 1121 CPNE1_P138_F 0.04 0.696 0.59 1122 RHOC_P536_F −0.05 0.698 0.59 1123 HDAC9_E38_F −0.05 0.698 0.59 1124 MYH11_P22_F −0.06 0.701 0.60 1125 CCND2_P898_R −0.07 0.701 0.60 1126 MMP19_P306_F −0.03 0.702 0.60 1127 RASSF1_P244_F −0.03 0.703 0.60 1128 THBS1_P500_F −0.03 0.703 0.60 1129 CTGF_E156_F −0.04 0.704 0.60 1130 IRAK3_E130_F −0.03 0.705 0.60 1131 TJP2_P518_F −0.03 0.706 0.60 1132 BCL3_P1038_R −0.03 0.709 0.60 1133 PI3_P274_R −0.03 0.709 0.60 1134 TNFRSF10A_P171_F −0.06 0.709 0.60 1135 PCDH1_E22_F −0.02 0.712 0.60 1136 PRSS1_E45_R −0.02 0.712 0.60 1137 MAS1_P657_R −0.03 0.712 0.60 1138 GFI1_P208_R 0.05 0.713 0.60 1139 FGF2_P229_F 0.05 0.716 0.60 1140 NQO1_E74_R −0.04 0.716 0.60 1141 DMP1_P134_F −0.02 0.718 0.60 1142 SFRP1_P157_F −0.04 0.719 0.60 1143 HSPA2_P162_R 0.02 0.720 0.60 1144 ZIM2_P22_F −0.02 0.720 0.60 1145 CALCA_E174_R −0.04 0.722 0.60 1146 HS3ST2_P546_F −0.02 0.722 0.60 1147 ESR2_P162_F −0.04 0.724 0.60 1148 KRT13_P341_R 0.03 0.725 0.60 1149 FGF3_P171_R 0.05 0.727 0.60 1150 TGFB2_P632_F 0.02 0.729 0.61 1151 MCM2_P260_F 0.02 0.730 0.61 1152 LIF_E208_F 0.02 0.732 0.61 1153 PCGF4_P92_R −0.06 0.733 0.61 1154 SEMA3C_P642_F 0.06 0.735 0.61 1155 ICAM1_P386_R 0.06 0.737 0.61 1156 MAP3K1_P7_F 0.03 0.737 0.61 1157 VIM_P343_R −0.05 0.737 0.61 1158 NTRK3_P752_F 0.04 0.738 0.61 1159 CTNNA1_P185_R 0.04 0.739 0.61 1160 NRG1_E74_F −0.05 0.739 0.61 1161 MMP7_P613_F 0.02 0.739 0.61 1162 SOX17_P303_F −0.02 0.739 0.61 1163 PEG3_E496_F 0.02 0.741 0.61 1164 CTSH_P238_F 0.04 0.743 0.61 1165 DKFZP564O0823_E4$$ −0.04 0.743 0.61 1166 HDAC11_P556_F 0.02 0.744 0.61 1167 PGR_E183_R −0.02 0.746 0.61 1168 ZNF215_P129_R −0.04 0.749 0.61 1169 LCN2_P86_R 0.03 0.750 0.61 1170 ABCC5_P444_F 0.03 0.751 0.61 1171 ABCA1_E120_R −0.02 0.751 0.61 1172 RBL2_P250_R −0.03 0.753 0.61 1173 SPDEF_P6_R 0.03 0.753 0.61 1174 TEK_E75_F −0.03 0.753 0.61 1175 PTPNS1_E433_R −0.04 0.755 0.61 1176 LIF_P383_R −0.03 0.756 0.61 1177 IL17RB_E164_R −0.05 0.757 0.61 1178 ABO_P312_F 0.03 0.757 0.61 1179 GAS7_E148_F −0.03 0.758 0.61 1180 RHOH_P121_F −0.04 0.759 0.61 1181 HSD17B12_E145_R −0.02 0.759 0.61 1182 COL18A1_P365_R −0.03 0.760 0.61 1183 IFNG_P459_R −0.02 0.762 0.61 1184 SERPINA5_P156_F −0.03 0.763 0.61 1185 CSF1R_P73_F 0.02 0.763 0.61 1186 FLI1_E29_F −0.02 0.764 0.61 1187 CDH17_P376_F 0.02 0.764 0.61 1188 ETS2_P835_F 0.03 0.764 0.61 1189 TERT_P360_R −0.02 0.767 0.61 1190 COL1A2_P48_R −0.03 0.767 0.61 1191 COL1A1_P5_F 0.04 0.767 0.61 1192 MEST_P4_F −0.06 0.768 0.61 1193 FGFR4_P610_F −0.02 0.768 0.61 1194 TFAP2C_E260_F −0.03 0.769 0.61 1195 DLC1_P88_R −0.03 0.771 0.62 1196 SLC5A8_E60_R 0.03 0.772 0.62 1197 LCN2_P141_R 0.03 0.774 0.62 1198 ITPR2_P804_F 0.04 0.775 0.62 1199 LRRK1_P834_F −0.02 0.775 0.62 1200 EGR4_E70_F −0.02 0.776 0.62 1201 RIPK4_E166_F −0.02 0.778 0.62 1202 EGF_P413_F 0.02 0.779 0.62 1203 MCC_P196_R −0.04 0.780 0.62 1204 ZIM3_P718_R −0.03 0.780 0.62 1205 PODXL_P1341_R −0.02 0.782 0.62 1206 CD82_P557_R 0.04 0.783 0.62 1207 WT1_P853_F −0.05 0.783 0.62 1208 HOXA5_E187_F 0.03 0.783 0.62 1209 TAL1_E122_F −0.04 0.784 0.62 1210 CDK6_P291_R −0.03 0.785 0.62 1211 TNFSF8_E258_R 0.05 0.785 0.62 1212 SEMA3A_P343_F 0.03 0.787 0.62 1213 MAGEL2_P170_R −0.02 0.788 0.62 1214 FGF8_E183_F 0.02 0.789 0.62 1215 TNFRSF10D_P70_F 0.02 0.789 0.62 1216 EPHB3_E0_F −0.03 0.791 0.62 1217 IL17RB_P788_R 0.05 0.791 0.62 1218 TRAF4_P372_F −0.02 0.791 0.62 1219 CTSH_E157_R −0.03 0.792 0.62 1220 IGF1_P933_F −0.01 0.797 0.62 1221 SPP1_E140_R 0.02 0.797 0.62 1222 FGF1_P357_R −0.02 0.798 0.62 1223 WRN_P969_F −0.02 0.800 0.62 1224 EGFR_P260_R −0.03 0.802 0.63 1225 CD44_P87_F −0.02 0.802 0.63 1226 FGF5_E16_F 0.03 0.807 0.63 1227 VAMP8_P241_F 0.02 0.808 0.63 1228 DLC1_P695_F −0.02 0.808 0.63 1229 CHGA_E52_F −0.02 0.809 0.63 1230 ERBB4_P255_F 0.04 0.809 0.63 1231 AXL_P223_R 0.03 0.810 0.63 1232 NTRK3_E131_F −0.02 0.810 0.63 1233 PROK2_E0_F −0.02 0.810 0.63 1234 HDAC1_P414_R 0.02 0.811 0.63 1235 IRAK3_P185_F 0.02 0.811 0.63 1236 TNC_P57_F 0.03 0.816 0.63 1237 ISL1_E87_R −0.02 0.818 0.63 1238 RAB32_P493_R −0.02 0.819 0.63 1239 TAL1_P594_F 0.03 0.819 0.63 1240 CEACAM1_E57_R 0.02 0.819 0.63 1241 SMO_E57_F 0.03 0.819 0.63 1242 NOS2A_E117_R −0.01 0.823 0.63 1243 LEFTY2_P561_F −0.02 0.823 0.63 1244 EGR4_P479_F 0.03 0.823 0.63 1245 GB2_P931_R 0.02 0.825 0.63 1246 MLH1_P381_F 0.02 0.826 0.63 1247 INS_P248_F 0.02 0.828 0.63 1248 IFNGR2_P377_R −0.02 0.829 0.63 1249 VAMP8_E7_F 0.02 0.831 0.63 1250 PROK2_P390_F 0.02 0.832 0.63 1251 IL1B_P829_F 0.02 0.832 0.63 1252 TNFRSF10C_E109_F −0.03 0.833 0.63 1253 TCF4_P317_F −0.03 0.834 0.64 1254 MMP9_P189_F −0.02 0.835 0.64 1255 ATP10A_P524_R 0.02 0.837 0.64 1256 NFKB1_P496_F −0.02 0.838 0.64 1257 PDGFRB_P343_F −0.02 0.838 0.64 1258 FGF12_E61_R −0.02 0.839 0.64 1259 ITGB4_E144_F −0.02 0.840 0.64 1260 PROM1_P44_R 0.02 0.841 0.64 1261 ICA1_P72_R −0.02 0.844 0.64 1262 EPHB2_E297_F −0.02 0.846 0.64 1263 SLC5A5_E60_F −0.02 0.847 0.64 1264 SERPINE1_P519_F −0.02 0.848 0.64 1265 DLK1_E227_R 0.02 0.849 0.64 1266 MATK_P190_R −0.01 0.850 0.64 1267 PTHR1_P258_F 0.01 0.851 0.64 1268 SMARCB1_P220_R −0.02 0.852 0.64 1269 BCL2L2_P280_F −0.03 0.855 0.64 1270 ST6GAL1_P164_R 0.03 0.855 0.64 1271 HBII-52_P563_F 0.01 0.857 0.64 1272 PTHLH_P15_R 0.02 0.863 0.65 1273 OSM_P188_F 0.02 0.864 0.65 1274 CDKN2B_E220_F 0.02 0.864 0.65 1275 CD9_E14_R −0.02 0.865 0.65 1276 TFPI2_P9_F 0.03 0.865 0.65 1277 PTPN6_P282_R −0.03 0.866 0.65 1278 IGF2_E134_R −0.03 0.866 0.65 1279 ETV1_P235_F −0.03 0.867 0.65 1280 ASCL2_P609_R 0.01 0.869 0.65 1281 ABCG2_P310_R 0.02 0.869 0.65 1282 MT1A_P600_F 0.01 0.870 0.65 1283 ZIM2_E110_F −0.01 0.870 0.65 1284 ZAP70_P220_R −0.01 0.871 0.65 1285 SFTPB_P689_R 0.01 0.871 0.65 1286 RUNX1T1_P103_F −0.02 0.871 0.65 1287 CEBPA_P1163_R −0.01 0.873 0.65 1288 DES_P1006_R 0.01 0.874 0.65 1289 HOXA5_P1324_F 0.02 0.875 0.65 1290 LTA_E28_R 0.02 0.876 0.65 1291 HFE_E273_R −0.02 0.877 0.65 1292 BMP2_P1201_F −0.03 0.877 0.65 1293 CCKBR_P361_R −0.01 0.878 0.65 1294 SH3BP2_P771_R −0.02 0.878 0.65 1295 NOTCH4_E4_F −0.02 0.879 0.65 1296 PADI4_E24_F 0.02 0.882 0.65 1297 PECAM1_E32_R −0.02 0.882 0.65 1298 MDR1_seq_42_S300 −0.02 0.886 0.65 1299 SGCE_P250_R 0.01 0.890 0.65 1300 ZP3_P220_F −0.01 0.890 0.65 1301 THBS2_P605_R −0.02 0.892 0.65 1302 S100A4_E315_F −0.01 0.892 0.65 1303 NPR2_P1093_F −0.01 0.893 0.65 1304 FLT1_E444_F −0.02 0.893 0.65 1305 FAS_P322_R −0.02 0.893 0.65 1306 PADI4_P1158_R 0.01 0.894 0.65 1307 AHR_P166_R 0.03 0.896 0.65 1308 NPR2_P618_F −0.01 0.897 0.65 1309 GUCY2D_E419_R 0.02 0.897 0.65 1310 APC_P14_F −0.01 0.899 0.66 1311 MMP3_P16_R −0.01 0.900 0.66 1312 MKRN3_E144_F 0.01 0.901 0.66 1313 IL4_P262_R 0.01 0.902 0.66 1314 PDGFA_P841_R 0.01 0.903 0.66 1315 PPP2R1B_P268_R −0.01 0.903 0.66 1316 WNT1_E157_F −0.02 0.904 0.66 1317 GABRG3_P75_F 0.01 0.906 0.66 1318 FLI1_P620_R −0.02 0.906 0.66 1319 FGFR1_E317_F 0.01 0.908 0.66 1320 TMEFF2_E94_R −0.01 0.909 0.66 1321 MUSK_P308_F −0.01 0.911 0.66 1322 MPL_P62_F 0.01 0.914 0.66 1323 RASSF1_E116_F 0.01 0.914 0.66 1324 CD34_P339_R −0.01 0.916 0.66 1325 CSF1R_E26_F −0.01 0.917 0.66 1326 BCR_P346_F 0.01 0.918 0.66 1327 CYP1A1_P382_F 0.02 0.919 0.66 1328 AREG_E25_F 0.01 0.919 0.66 1329 PTHLH_E251_F 0.01 0.921 0.66 1330 SPDEF_E116_R 0.01 0.921 0.66 1331 ACVR1B_E497_R −0.02 0.921 0.66 1332 HSD17B12_P97_F −0.01 0.922 0.66 1333 ICAM1_E242_F −0.01 0.922 0.66 1334 FER_P581_F −0.01 0.922 0.66 1335 LTB4R_P163_F 0.01 0.927 0.66 1336 APP_P179_R 0.01 0.927 0.66 1337 TNF_P1084_F −0.01 0.928 0.66 1338 GRB7_P160_R −0.01 0.928 0.66 1339 MMP3_P55_F 0.00 0.928 0.66 1340 PARP1_P610_R −0.01 0.929 0.66 1341 TK1_P62_R 0.01 0.931 0.66 1342 EPHB1_P503_F 0.01 0.932 0.66 1343 ASCL2_P360_F −0.01 0.932 0.66 1344 ALPL_P278_F 0.01 0.933 0.66 1345 SEZ6L_P249_F −0.01 0.939 0.67 1346 IGSF4_P454_F 0.01 0.940 0.67 1347 MLLT4_P1400_F −0.01 0.940 0.67 1348 NKX3-1_P146_F 0.01 0.942 0.67 1349 CASP2_P192_F 0.01 0.942 0.67 1350 IGFBP2_P306_F 0.01 0.943 0.67 1351 IPF1_P750_F −0.01 0.943 0.67 1352 RASA1_E107_F 0.01 0.945 0.67 1353 PRKCDBP_P352_R −0.01 0.945 0.67 1354 FGF3_E198_R −0.01 0.946 0.67 1355 MDS1_E45_F 0.01 0.948 0.67 1356 CDK10_E74_F 0.00 0.949 0.67 1357 THPO_P585_R 0.00 0.951 0.67 1358 MMP7_E59_F 0.01 0.951 0.67 1359 IFNG_P188_F 0.00 0.951 0.67 1360 HPSE_P29_F 0.00 0.952 0.67 1361 PSCA_E359_F 0.01 0.953 0.67 1362 AGTR1_P154_F −0.01 0.953 0.67 1363 PURA_P928_R 0.02 0.954 0.67 1364 PTK2_P735_R −0.01 0.956 0.67 1365 MEG3_E91_F 0.00 0.956 0.67 1366 SYK_E372_F 0.00 0.956 0.67 1367 EGF_E339_F 0.00 0.957 0.67 1368 SEPT9_P374_F −0.01 0.957 0.67 1369 TBX1_P520_F 0.01 0.958 0.67 1370 HIC1_P565_R 0.01 0.958 0.67 1371 CLK1_P538_F 0.00 0.958 0.67 1372 EDN1_E50_R 0.01 0.959 0.67 1373 CSF3R_P472_F 0.01 0.960 0.67 1374 TNK1_P41_R −0.01 0.961 0.67 1375 MC2R_P1025_F 0.00 0.961 0.67 1376 SHH_P104_R 0.00 0.961 0.67 1377 IL10_P85_F 0.01 0.961 0.67 1378 STAT5A_P704_R 0.01 0.962 0.67 1379 CSF3_E242_R 0.00 0.963 0.67 1380 DDB2_P613_R 0.01 0.963 0.67 1381 MCAM_P169_R −0.01 0.964 0.67 1382 TEK_P526_F 0.00 0.966 0.67 1383 TRIP6_P1274_R 0.00 0.966 0.67 1384 EMR3_E61_F 0.00 0.966 0.67 1385 MME_P388_F −0.01 0.968 0.67 1386 CCNC_P132_R 0.00 0.969 0.67 1387 MYBL2_P354_F 0.00 0.970 0.67 1388 TMEFF1_E180_R 0.00 0.974 0.67 1389 FHIT_P93_R −0.01 0.975 0.67 1390 ERBB2_P59_R 0.00 0.975 0.67 1391 ETV6_E430_F −0.01 0.976 0.67 1392 RET_seq_53_S374_F 0.00 0.977 0.67 1393 VEGFB_P658_F 0.00 0.977 0.67 1394 CALCA_P75_F 0.00 0.980 0.67 1395 NAT2_P11_F 0.00 0.981 0.67 1396 SCGB3A1_E55_R 0.00 0.982 0.67 1397 BMP2_E48_R 0.00 0.983 0.67 1398 CREBBP_P712_R 0.00 0.984 0.67 1399 BCL2A1_P1127_R 0.00 0.984 0.67 1400 ACVR1C_P363_F 0.00 0.985 0.67 1401 CDH11_P203_R 0.00 0.986 0.67 1402 LMO2_E148_F 0.00 0.987 0.67 1403 B3GALT5_E246_R 0.00 0.987 0.67 1404 HLA-DPA1_P205_R 0.00 0.989 0.67 1405 SEMA3F_P692_R 0.00 0.990 0.67 1406 EPHA8_P456_R 0.00 0.990 0.67 1407 TRIP6_E33_F 0.00 0.991 0.67 1408 LMTK2_P1034_F 0.00 0.993 0.67 1409 MAD2L1_E93_F 0.00 0.998 0.68 1410 ICA1_P61_F 0.00 0.999 0.68 1411 TK1_E47_F 0.00 0.999 0.68 1412 VAV1_P317_F 0.00 1.000 0.68 1413 *Negative regression coefficient indicates reduced methylation in infant bloods from case 

1. A method for the diagnosis or prognosis of cancer in a subject comprising (a) obtaining DNA methylation data from DNA of a subject's cells wherein said cells are suspected of being cancerous (Subject DNA methylation data); (b) comparing said Subject DNA methylation data to a library of Tumor Control DNA methylation data and a library of Normal Control DNA methylation data (each representing same tissue of origin); (c) fitting by mixture modeling P(Y,C) Subject DNA methylation data to said Tumor and Normal Control DNA methylation data using recursively partitioned mixture modeling (RPMM) in conjunction with an empirical Bayes procedure generating a posterior probability distribution P(C|y*) of methylation class membership for Subject DNA y*, said Subject DNA methylation data's identity with Normal Control being indicated by posterior probability of membership P(C=k|y*) at least 90% in a class k comprised of at least 95% Normal Control samples [P(control|C=k)>95%]; (d) establishing a metric-based criterion for comparison by computing mean methylation average beta values μ_(j) at each CpG locus j from said Normal Control DNA methylation samples data y_(ij) and fitting the distribution of squared weighted Euclidean distances d_(i) ²=Σ{(y_(ij)−μ_(j))²/[μ_(j)(1−μ_(j))]} to a gamma distribution G, and where said Subject DNA methylation data's squared weighted Euclidean distance d*²=Σ{(y_(j)*−μ_(j))²/[μ_(j)(1−μ_(j))]} is less than the 95% quantile of G it is indicated with at least 95% certainty that the subject's sample is Normal and if the subject's squared weighted Euclidian distance d*² is greater than the 95% quantile of G it is indicated with at least 95% certainty that the subject's sample is a cancer.
 2. The method of claim 1 wherein the subject's sample is determined to be cancer further comprising determining said subject's prognosis by applying steps (c)/(d) above to said Tumor Control DNA methylation sample data only said methylation data was derived having distribution of class membership greater than about 90%.
 3. The method of claim 1 for the diagnosis or prognosis of malignant pleural mesothelioma.
 4. The method of claim 1 for the diagnosis or prognosis of lung adenocarcinoma.
 5. The method of claim 1 for the differential diagnosis of cancer type.
 6. The method of claim 5 for differential diagnosis of malignant pleural mesothelioma, lung adenocarcinoma, and normal lung tissue.
 7. The method of claim 1 for the diagnosis or prognosis of head and neck squamous cell carcinoma.
 8. The method of claim 1 for determining the risk of a newborn infant developing leukemia.
 9. The method of claim 7 further wherein said risk is determined as to leukemia subtype or prognosis.
 10. The method of claim 1 wherein said diagnosis or prognosis is determining the epigenetic signature of differentiated blood cells. 